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Antineoplastic agents l

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  • Labetuzumab govitecan - An antibody-drug conjugate (ADC) containing labetuzumab, a mildly reduced, anti-CEACAM5 humanized monoclonal antibody, conjugated to the potent topoisomerase I inhibitor SN-38, with antineoplastic activity. The monoclonal antibody moiety of labetuzumab govitecan selectively binds to carcinoembryonic cell adhesion molecule 5 (CEACAM5), which is abundantly expressed on the surface of a majority of solid tumors. Upon internalization and proteolytic cleavage, SN-38, the active metabolite of irinotecan, inhibits the activity of topoisomerase I in the tumor cells, eventually inhibiting both DNA replication and transcription and leading to tumor cell apoptosis.
  • Lacutamab - A humanized monoclonal antibody against the immune receptor human killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 2 (KIR3DL2), with potential immunomodulating and antineoplastic activities. Upon administration, lacutamab binds to KIR3DL2 expressed on certain tumor cells. This recruits natural killer (NK) cells and leads to lysis of KIR3DL2-expressing tumor cells. In addition, IPH4102 induces antibody-dependent cellular cytotoxicity (ADCC), thereby further eliminating tumor cells. KIR3DL2, a tumor-associated antigen (TAA) and inhibitory receptor of the KIR family, is specifically expressed in most subtypes of cutaneous T-cell lymphomas (CTCL) and expressed only on a fraction of normal NK cells.
  • Ladiratuzumab vedotin - An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody directed against the anti-solute carrier family 39 zinc transporter member 6 (SLC39A6; LIV-1; ZIP6) protein that is conjugated, via a protease-cleavable linker, to the cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration and internalization by LIV-1-positive tumor cells, ladiratuzumab vedotin undergoes enzymatic cleavage to release MMAE into the cytosol. In turn, MMAE binds to and inhibits tubulin polymerization, which may result in G2/M phase cell cycle arrest and apoptosis in LIV-1-expressing tumor cells. LIV-1, a member of the zinc transporter family, is expressed in several types of solid tumors and plays a key role in tumor cell progression and metastasis. The linkage system in ladiratuzumab vedotin is highly stable in plasma, resulting in cytotoxic specificity against LIV-1-positive cells.
  • Ladirubicin - A 4-demethoxydaunorubicin (idarubicin) analog with an aziridinyl group in position C-3' and a methylsulphonyl on position C-4', with potential antineoplastic activity. Upon intravenous administration, ladirubicin alkylates guanine residues at the N7 position in the DNA major groove, resulting in DNA base pair mismatching, DNA interstrand crosslinking, the inhibition of DNA repair and synthesis, cell-cycle arrest, and apoptosis.
  • Laetrile - Originally, the name laetrile was the contraction of laevo-mandelonitrile glucoside, a cyanogenic glycoside found naturally in some plants. Over the years the meaning of laetrile has changed. There are now preparations called Laetrile where amygdalin is the major constituent. Laetrile and amygdalin are often used interchangeably, but are different agents. Cyanide and benzaldehyde are metabolites of both laetrile and amygdalin. Both metabolites may possess antineoplastic properties. Laetrile has been used as an anticancer treatment in humans worldwide, but scientific evidence does not support its effectiveness. It is not approved for use in the United States.
  • Lair-2 fusion protein nc410 - A fusion protein of leukocyte-associated immunoglobulin (Ig)-like receptor (LAIR)-2, a high-affinity collagen receptor, with potential immunomodulatory and antineoplastic activities. Upon administration, LAIR-2 fusion protein NC410 binds to the ligand collagen of LAIR-1 (CD305), thereby blocking the binding of LAIR-1 to its ligand collagen and inhibiting LAIR-1-mediated immune suppression. This may result in enhanced T-cell and dendritic cell (DC) activities, and cytotoxic T-lymphocyte (CTL) and anti-tumor immune responses. LAIR-1, a collagen-receptor and an inhibitory immune receptor belonging to the Ig superfamily, is expressed on many peripheral blood mononuclear cells (PBMC) including T-cells and DCs.
  • Landogrozumab - A monoclonal antibody against myostatin (MSTN) with potential anti-cachexia activity. Upon administration, landogrozumab binds to and neutralizes the MSTN protein, thereby blocking the MSTN signalling pathway. This may help decrease muscle protein breakdown and muscle weakness and may attenuate cancer cachexia. MSTN, a member of the transforming growth factor-beta (TGF-beta) superfamily, is a negative regulator of muscle growth and development.
  • Laniquidar - A stereoisomer of verapamil and third-generation P-glycoprotein inhibitor. Laniquidar inhibits the drug efflux pump P-glycoprotein, resulting in higher concentrations of antineoplastic agents in tumor cells that are multi-drug resistant due to the overexpression of P-glycoprotein.
  • Lanreotide acetate - The acetate salt of a synthetic cyclic octapeptide analogue of somatostatin. Lanreotide binds to somatostatin receptors (SSTR), specifically SSTR-2 and also to SSTR-5 with a lesser affinity. However, compare with octreotide, this agent is less potent in inhibiting the release of growth hormone from the pituitary gland. Furthermore, lanreotide has an acute effect on decreasing circulating total and free insulin-like growth factor 1 (IGF-I). This agent is usually given as a prolonged-release microparticle or Autogel formulation for the treatment of acromegaly and to relieve the symptoms of neuroendocrine tumors.
  • Lapachone - A poorly soluble, ortho-naphthoquinone with potential antineoplastic and radiosensitizing activity. Beta-lapachone (b-lap) is bioactivated by NAD(P)H:quinone oxidoreductase-1 (NQO1), creating a futile oxidoreduction that generates high levels of superoxide. In turn, the highly reactive oxygen species (ROS) interact with DNA, thereby causing single-strand DNA breaks and calcium release from endoplasmic reticulum (ER) stores. Eventually, the extensive DNA damage causes hyperactivation of poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme facilitating DNA repair, accompanied by rapid depletion of NAD+/ATP nucleotide levels. As a result, a caspase-independent and ER-stress induced mu-calpain-mediated cell death occurs in NQO1-overexpressing tumor cells. NQO1, a flavoprotein and two-electron oxidoreductase, is overexpressed in a variety of tumors.
  • Lapatinib - A synthetic, orally-active quinazoline with potential antineoplastic properties. Lapatinib reversibly blocks phosphorylation of the epidermal growth factor receptor (EGFR), ErbB2, and the Erk-1 and-2 and AKT kinases; it also inhibits cyclin D protein levels in human tumor cell lines and xenografts. EGFR and ErbB2 have been implicated in the growth of various tumor types.
  • Lapatinib ditosylate - The ditosylate salt of lapatinib, a synthetic, orally-active quinazoline with potential antineoplastic activity. Lapatinib reversibly blocks phosphorylation of the epidermal growth factor receptor (EGFR), ErbB2, and the Erk-1 and-2 and AKT kinases; it also inhibits cyclin D protein levels in human tumor cell lines and xenografts. EGFR and ErbB2 have been implicated in the growth of various tumor types.
  • Laprituximab emtansine - A targeted antibody payload (TAP)-based immunoconjugate consisting of a human monoclonal antibody directed against the epidermal growth factor receptor (EGFR) conjugated, via a nonreducible thioether linker (succinimidyl trans-4-(maleimidylmethyl)cyclohexane-1-carboxylate or SMCC), to the cytotoxic agent maytansinoid mertansine (DM1), with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of laprituximab emtansine binds to and inhibits EGFR on tumor cell surfaces. Inhibition of EGFR prevents EGFR-mediated signaling and may inhibit tumor cell proliferation. After internalization, the mertansine moiety binds to tubulin and interferes with microtubule assembly/disassembly dynamics. This inhibits both cell division and the proliferation of cancer cells that express EGFR. EGFR, overexpressed by a variety of cancers, plays a key role in tumor cell proliferation and survival. Linkage of the antibody and drug, through a nonreducible linker, appears to contribute to the improved efficacy and reduced toxicity of this antibody-drug conjugate (ADC) compared to similar ADCs constructed with reducible linkers.
  • Lapuleucel-t - A cell-based vaccine targets tumors expressing the HER2/neu marker. HER-2/neu is a growth factor receptor, and its overexpression has been associated with a number of cancers including breast, ovarian, colon and lung cancers. APC8024 comprise of autologous antigen-presenting peripheral blood mononuclear cells (APCs) that have been exposed to HER2/neu protein and can be administered to the patient. These cells may stimulate an antitumor T-cell response to cancer cells expressing HER2/neu.
  • Laromustine - A sulfonyl hydrazine prodrug with antineoplastic activity. Laromustine releases the DNA chloroethylating agent 90CE after entering the blood stream; 90CE chloroethylates alkylates the O6 position of guanine, resulting in DNA crosslinking, strand breaks, chromosomal aberrations, and disruption of DNA synthesis. Intracellular metabolism of this agent also releases methyl isocyanate which inhibits O6-alkyl-guanine transferase, an enzyme involved with DNA repair.
  • Larotaxel - A semi-synthetic derivative of the taxane 10-deacetylbaccatin III with potential antineoplastic activities. Larotaxel binds to tubulin, promoting microtubule assembly and stabilization and preventing microtubule depolymerization, thereby inhibiting cell proliferation. As it represents poor substrate for P-glycoprotein-related drug resistance mechanisms, this agent may be useful for treating multi-drug resistant tumors. Larotaxel penetrates the blood brain barrier.
  • Larotinib mesylate - The mesylate salt form of larotinib, a reversible pan-ErbB inhibitor with potential antineoplastic activity. Upon administration, larotinib binds to and inhibits ErbB tyrosine receptor kinases, which may result in the inhibition of cellular proliferation and angiogenesis in tumors expressing ErbB. The ErbB protein family, also called the epidermal growth factor receptor (EGFR) family, plays major roles in tumor cell proliferation and tumor vascularization.
  • Larotrectinib - An orally available, tropomyosin receptor kinase (Trk) inhibitor, with potential antineoplastic activity. Upon administration, larotrectinib binds to Trk, thereby preventing neurotrophin-Trk interaction and Trk activation, which results in both the induction of cellular apoptosis and the inhibition of cell growth in tumors that overexpress Trk. Trk, a receptor tyrosine kinase activated by neurotrophins, is mutated in a variety of cancer cell types and plays an important role in tumor cell growth and survival.
  • Larotrectinib sulfate - The sulfate salt form of larotrectinib, an orally available, tropomyosin receptor kinase (Trk) inhibitor, with potential antineoplastic activity. Upon administration, larotrectinib binds to Trk, thereby preventing neurotrophin-Trk interaction and Trk activation, which results in both the induction of cellular apoptosis and the inhibition of cell growth in tumors that overexpress Trk. Trk, a receptor tyrosine kinase activated by neurotrophins, is mutated in a variety of cancer cell types and plays an important role in tumor cell growth and survival.
  • Lavendustin a - A compound isolated from strains of Streptomyces griseolavendus that may exert antitumor activity by inhibition of protein tyrosine kinase and tubulin polymerization. (NCI)
  • Lazertinib - An orally available third-generation, selective inhibitor of certain forms of the epidermal growth factor receptor (EGFR) with activating mutations, including the resistance mutation T790M, exon 19 deletions (Del19), and the L858R mutation, with potential antineoplastic activity. Upon administration, lazertinib specifically and irreversibly binds to and inhibits selective EGFR mutants, which prevents EGFR mutant-mediated signaling and leads to cell death in EGFR mutant-expressing tumor cells. Lazertinib may inhibit programmed cell death-1 ligand 1 (PD-L1) and inflammatory cytokines in specific cancer cells harboring certain EGFR mutations. Compared to some other EGFR inhibitors, lazertinib may have therapeutic benefits in tumors with T790M- or L858R-mediated drug resistance. In addition, lazertinib penetrates the blood-brain barrier (BBB). This agent shows minimal activity against wild-type EGFR (wtEGFR), and does not cause dose-limiting toxicities, which occur during the use of non-selective EGFR inhibitors and inhibit wtEGFR. EGFR, a receptor tyrosine kinase (RTK) mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.
  • Lead pb 212 tcmc-trastuzumab - A radioimmunoconjugate containing the recombinant humanized monoclonal antibody trastuzumab conjugated with the bifunctional chelating agent TCMC ((1,4,7,10-Tetra-(2-Carbamoyl Methyl)-Cyclododecane), and radiolabeled with the alpha-emitting isotope lead Pb 212, with potential anti-tumor activity. Upon administration, the antibody moiety of lead Pb 212 TCMC-trastuzumab binds with high affinity to the extracellular domain of human epidermal growth factor receptor 2 (HER2); after internalization, the radioisotope moiety delivers a cytotoxic dose of alpha radiation to the HER2-expressing tumor cells. HER2, a tyrosine kinase receptor, is overexpressed on the cell surface of a variety of cancer cell types.
  • Lefitolimod - A synthetic oligonucleotide based on a proprietary double stem-loop immunomodulator design with potential immunostimulating activity. Lefitolimod binds to and activates intracellular Toll-like receptor 9 (TLR9) in monocytes/macrophages, plasmacytoidal and myeloid dendritic cells (DCs), and natural killer (NK) cells, initiating immune signaling pathways and inducing T-helper 1 cell (Th1) production leading to the production of memory T cells and a Th1-mediated immune response. By activating the immune system, MGN1703 may attack tumor associated antigen (TAAs). TLR9 is a member of the TLR family, which plays a fundamental role in pathogen recognition and activation of innate immunity.
  • Leflunomide - A derivative of isoxazole used for its immunosuppressive and anti-inflammatory properties. As a prodrug, leflunomide is converted to an active metabolite, A77 1726, which blocks dihydroorotate dehydrogenase, a key enzyme of de novo pyrimidine synthesis, thereby preventing the expansion of activated T lymphocytes. This agent also inhibits various protein tyrosine kinases, such as protein kinase C (PKC), thereby inhibiting cell proliferation.
  • Lenalidomide - A thalidomide analog with potential antineoplastic activity. Lenalidomide inhibits TNF-alpha production, stimulates T cells, reduces serum levels of the cytokines vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and inhibits angiogenesis. This agent also promotes G1 cell cycle arrest and apoptosis of malignant cells.
  • Lenalidomide analog kpg-121 - A lenalidomide analog with potential anti-angiogenic and immunomodulatory activities. Upon oral administration, lenalidomide analog KPG-121 may inhibit tumor necrosis factor alpha (TNF-alpha) production, stimulate T-lymphocytes, reduce serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF; FGF2), and inhibit angiogenesis. Additionally, KPG-121 may promote G1 cell cycle arrest and induce apoptosis in malignant cells.
  • Lentivirus vector rhiv7-shi-tar-ccr5rz-transduced hematopoietic progenitor cells - Autologous, CD34-positive hematopoietic progenitor cells (HPCs) transduced with rHIV7-shI-TAR-CCR5RZ, a lentiviral vector encoding three anti-human immunodeficiency virus (HIV) RNA genes, with potential antineoplastic activity. The 3 RNA products produced by the lentilvirus are: a short hairpin RNA (shRNA) targeted to an exon of the HIV-1 genes tat/rev, designated as shI; a decoy for the HIV TAT reactive element, designated as TAR; a ribozyme targeting the host cells CCR5 chemokine receptor, designated as CCR5RZ. Upon administration, lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells expressing the 3 species of RNAs display 3 seperate mechanims of action: the shRNA blocks the transcription of tat/rev, the TAR decoy binds to the TAT protein that is essential for HIV replication, and CCR5RZ catalyzes CCR5 which is needed for viral attachment and entry into the host cells. Altogether, infusion of these HPCs may ultimately inhibit HIV replication and suppress HIV infection.
  • Lenvatinib - A synthetic, orally available inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR/FLK-1) tyrosine kinase with potential antineoplastic activity. Lenvatinib blocks VEGFR2 activation by VEGF, resulting in inhibition of the VEGF receptor signal transduction pathway, decreased vascular endothelial cell migration and proliferation, and vascular endothelial cell apoptosis.
  • Lenvatinib mesylate - A synthetic, orally available inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR/FLK-1) tyrosine kinase with potential antineoplastic activity. E7080 blocks VEGFR2 activation by VEGF, resulting in inhibition of the VEGF receptor signal transduction pathway, decreased vascular endothelial cell migration and proliferation, and vascular endothelial cell apoptosis.
  • Lenzilumab - A recombinant monoclonal antibody against the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF), with potential immunomodulating activity. Upon administration, lenzilumab binds to and neutralizes GM-CSF. This prevents GM-CSF binding to the GM-CSF receptor, which is a heterodimeric protein expressed on myeloid progenitor cells, and prevents GM-CSF-mediated signaling. This may induce apoptosis in and inhibit proliferation of cancer cells that overproduce GM-CSF. GM-CSF plays a key role in the differentiation and proliferation of monocytes, macrophages and granulocytes; elevated levels of GM-CSF are associated with certain autoimmune diseases, inflammatory diseases, and cancers.
  • Lerociclib - An orally bioavailable inhibitor of cyclin-dependent kinase (CDK) types 4 (CDK4) and 6 (CDK6), with potential antineoplastic activity. Upon administration, lerociclib selectively inhibits CDK4 and CDK6, which inhibits the phosphorylation of retinoblastoma protein (Rb) early in the G1 phase, prevents CDK-mediated G1-S phase transition and leads to cell cycle arrest. This suppresses DNA replication and decreases tumor cell proliferation. CDK4 and 6 are serine/threonine kinases that are upregulated in many tumor cell types and play a key role in the regulation of both cell cycle progression from the G1-phase into the S-phase and tumor cell proliferation.
  • Lestaurtinib - An orally bioavailable indolocarbazole derivative with antineoplastic properties. Lestaurtinib inhibits autophosphorylation of FMS-like tyrosine kinase 3 (FLT3), resulting in inhibition of FLT3 activity and induction of apoptosis in tumor cells that overexpress FLT3. (NCI05)
  • Letetresgene autoleucel - Human autologous T-lymphocytes transduced with a lentiviral vector encoding a T-cell receptor (TCR) specific for the cancer-testis antigens (CTAs) NY-ESO-1 and L antigen family member 1 (LAGE-1; Cancer/Testis Antigen 2; CTAG2; CT2), with potential antineoplastic activity. Following leukapheresis, isolation of lymphocytes, expansion ex vivo, transduction, and reintroduction into the patient, letetresgene autoleucel specifically target and bind to NY-ESO-1/LAGE-1-overexpressing tumor cells. This may result in a cytotoxic T-lymphocyte (CTL)-mediated elimination of NY-ESO-1/LAGE-1-positive cancer cells. NY-ESO-1 and LAGE-1, members of the cancer-testis antigen (CTA) family, are overexpressed on the surface of various tumor cell types.
  • Letolizumab - A dimeric fusion protein composed of the C-terminus of the domain antibody (dAb) BMS2h-572-633 targeting the CD40 ligand (CD40L or CD154) linked to a modified Fc fragment of immunoglobulin G1 (IgG1), with potential immunomodulatory activity. Upon intravenous administration, the peptide moiety of letolizumab specifically targets and binds to CD40L expressed on T-lymphocytes. This prevents the binding of CD40L to its cognate receptor CD40 expressed on B-lymphocytes, macrophages, and dendritic cells (DCs). This prevents T-cell mediated proliferation and differentiation of B-cells, and prevents the production of antibodies. By inhibiting both the production of anti-glycoprotein (GP) IIb/IIIa antibodies by B-cells and GPIIb/IIIa-dependent T-cell proliferation, letolizumab may prevent platelet destruction and may increase platelet counts in idiopathic thrombocytopenic purpura (ITP). The direct binding of letolizumab to CD40L on platelets further prevents CD40L/CD40-mediated destruction by macrophages and DCs in ITP. The modified Fc domain prevents the binding of letolizumab to the Fc receptor FcgammaRIIA on platelets, thereby preventing FcgammaRIIA-dependent platelet activation and anti-CD40L-induced thromboembolism. CD40L, a transmembrane protein of the tumor necrosis factor (TNF) superfamily, is primarily expressed on activated T-cells, but is also expressed on eosinophils, basophils, natural killer (NK) cells, mast cells, platelets and activated endothelial cells.
  • Letrozole - A nonsteroidal inhibitor of estrogen synthesis with antineoplastic activity. As a third-generation aromatase inhibitor, letrozole selectively and reversibly inhibits aromatase, which may result in growth inhibition of estrogen-dependent breast cancer cells. Aromatase, a cytochrome P-450 enzyme localized to the endoplasmic reticulum of the cell and found in many tissues including those of the premenopausal ovary, liver, and breast, catalyzes the aromatization of androstenedione and testosterone into estrone and estradiol, the final step in estrogen biosynthesis.
  • Leucovorin calcium - An active metabolite of folic acid (also called folinic acid and citrovorum factor), which does not require metabolism by dihydrofolate reductase, the molecular target of folate antagonist-type chemotherapeutic drugs. Leucovorin calcium counteracts the toxic effects of these medications, 'rescuing' the patient while permitting the antitumor activity of the folate antagonist. This agent also potentiates the effects of fluorouracil and its derivatives by stabilizing the binding of the drug's metabolite to its target enzyme, thus prolonging drug activity.
  • Leukemic apoptotic corpse-pulsed autologous dendritic cells - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with corpses of apoptotic leukemic cells, with potential immunostimulatory and antineoplastic activities. Upon vaccination, autologous dendritic cells pulsed with leukemic apoptotic corpse may activate the immune system to mount an anti-tumoral cytotoxic T-lymphocyte (CTL) response against leukemic cells expressing leukemia-associated antigens, which may result in leukemic cell lysis and inhibition of tumor cell growth. Apoptotic tumor cell corpses contain an array of tumor associated antigens (TAAs).
  • Leuprolide - A synthetic nonapeptide analogue of gonadotropin-releasing hormone. Leuprolide binds to and activates gonadotropin-releasing hormone (GnRH) receptors. Continuous, prolonged administration of leuprolide in males results in pituitary GnRH receptor desensitization and inhibition of pituitary secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH), leading to a significant decline in testosterone production; in females, prolonged administration results in a decrease in estradiol production. This agent reduces testosterone production to castration levels and may inhibit androgen receptor-positive tumor progression.
  • Leuprolide acetate - The acetate salt of a synthetic nonapeptide analogue of gonadotropin-releasing hormone. Leuprolide binds to and activates gonadotropin-releasing hormone (GnRH) receptors. Continuous, prolonged administration of leuprolide in males results in pituitary GnRH receptor desensitization and inhibition of pituitary secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH), leading to a significant decline in testosterone production; in females, prolonged administration results in a decrease in estradiol production. This agent reduces testosterone production to castration levels and may inhibit androgen receptor-positive tumor progression.
  • Leuprolide mesylate injectable suspension - A depot suspension for injection composed of the mesylate salt of leuprolide, a synthetic, long-acting nonapeptide analog of the endogenous hormone gonadotropin-releasing hormone (GnRH), with potential antineoplastic activity. Upon subcutaneous injection of the depot suspension, leuprolide binds to and activates the gonadotropin-releasing hormone receptor (GnRHR). The continuous stimulation of GnRHR by leuprolide results in both the desensitization of pituitary GnRHR and the inhibition of pituitary secretion of the gonadotropins follicle stimulating hormone (FSH) and luteinizing hormone (LH). In males, this results in a significant decline in testosterone production to castration levels and may inhibit androgen receptor-positive tumor progression.
  • Leurubicin - An N-L-leucyl prodrug of the anthracycline doxorubicin, with antineoplastic activity. Leurubicin is converted to its active form doxorubicin in or on tumor cells by hydrolytic enzymes.
  • Lexatumumab - A fully human monoclonal agonistic antibody directed against tumor necrosis factor-alpha (TNF-alpha)-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) with potential antitumor activity. Mimicking the natural ligand TRAIL, lexatumumab binds to and activates TRAIL-R2, which may trigger apoptosis in and inhibit the growth of TRAIL-R2-expressing tumor cells. TRAIL-R2, also known as death receptor 5 (DR5), is a member of the TNF receptor family and is expressed on many malignant cell types.
  • Lexibulin - An orally bioavailable small-molecule with tubulin-inhibiting, vascular-disrupting, and potential antineoplastic activities. Lexibulin inhibits tubulin polymerization in tumor blood vessel endothelial cells and tumor cells, blocking the formation of the mitotic spindle and leading to cell cycle arrest at the G2/M phase; this may result in disruption of the tumor vasculature and tumor blood flow, and tumor cell death.
  • L-gossypol - The levo-enantiomer of an orally bioavailable polyphenolic aldehyde, derived primarily from unrefined cottonseed oil, with potential antineoplastic activity. Mimicking the inhibitory BH3 (Bcl-2 homology 3) domain of endogenous antagonists of Bcl-2, L-gossypol binds to and inhibits various anti-apoptotic Bcl-2 proteins, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. This agent has greater affinity for Bcl-2 proteins than racemic gossypol.
  • Liarozole - An orally-active benzimidazole derivative with potential antineoplastic activity. As a retinoic acid metabolism blocking agent, liarozole inhibits cytochrome P450-dependent all-trans-retinoic acid (ATRA)-4-hydroxylase, resulting in an increase in endogenous ATRA production, inhibition of cell proliferation, and induction of cell differentiation. This agent also inhibits aromatase, the enzyme that catalyzes the final, rate-limiting step in estrogen biosynthesis.
  • Liarozole fumarate - The orally active fumarate salt of the benzimidazole derivative liarozole with potential antineoplastic activity. As a retinoic acid metabolism blocking agent (RAMBA), liarozole inhibits cytochrome P450-dependent all-trans-retinoic acid (ATRA)-4-hydroxylase, resulting in an increase in endogenous ATRA production, inhibition of cell proliferation, and induction of cell differentiation. This agent also inhibits aromatase, the enzyme that catalyzes the final, rate-limiting step in estrogen biosynthesis.
  • Liarozole hydrochloride - The fumarate salt of an orally-active benzimidazole derivative with potential antineoplastic activity. As a retinoic acid metabolism blocking agent (RAMBA), liarozole inhibits cytochrome P450-dependent all-trans-retinoic acid (ATRA)-4-hydroxylase, resulting in an increase in endogenous ATRA production, inhibition of cell proliferation, and induction of cell differentiation. This agent also inhibits aromatase, the enzyme that catalyzes the final, rate-limiting step in estrogen biosynthesis.
  • Licartin - An immunoradioconjugate containing metuximab, an antibody fragment targeting the hepatocellular cancer (HCC)-associated antigen HAb18G/CD147, that is conjugated to the radioisotope iodine I 131, with potential antineoplastic activity. Upon administration, the metuximab moiety of licartin targets and binds to HAb18G/CD147 on HCC cells; upon internalization, the radioisotope I 131 delivers a cytotoxic dose of gamma radiation, thereby causing selective destruction of HAb18G/CD147-expressing cells. HAb18G/CD147, a member of CD147 family, is overexpressed in HCC and fibroblasts and its expression is associated with cancer cell progression and increased adhesion, invasion and metastasis.
  • Licorice - An herbal extract derived from the root of the plant Glycyrrhiza glabra with potential anti-inflammatory, antioxidant, and antineoplastic activities. Licorice root extract contains glycoside glycyrrhizinic acid and numerous flavonoids. Glycyrrhizinic acid in licorice root extract is hydrolyzed to glycyrrhetic acid (GA); GA inhibits 11 beta-hydroxysteroid dehydrogenase, resulting in inhibition of the conversion of cortisol to the inactive steroid cortisone and elevated cortisol levels. In addition, GA inhibits 17,20-lyase and 17 beta-hydroxysteroid dehydrogenase, resulting in decreased conversions of 17-hydroxyprogesterone to androstenedione and androstenedione to testosterone. The primary antioxidant found in licorice root, the flavonoid glabridin, may inactivate or inhibit the activities of some cytochrome P450 enzymes. In tumor cells, beta-hydroxy-DHP, another flavonoid, may induce Bcl-2 phosphorylation, apoptosis, and G2/M cell cycle arrest.
  • Lifastuzumab vedotin - An antibody-drug conjugate (ADC) composed of a monoclonal antibody directed against the sodium-dependent phosphate transport protein 2B (NaPi2b), and covalently linked to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule disrupting agent, with potential antineoplastic activity. Upon administration, the monoclonal antibody moiety of DNIB0600A binds to NaPi2b-expressing tumor cells and is internalized, thereby delivering MMAE intracellularly. Proteolytic cleavage releases MMAE, which then binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. NaPi2b, a tumor-associated antigen (TAA), overexpressed in a variety of cancer cell types, plays a key role in transport of inorganic phosphate and the maintenance of phosphate homeostasis.
  • Lifileucel - A preparation of autologous tumor infiltrating lymphocytes (TILs), with potential antineoplastic activity. TILs are isolated from a patient's tumor tissue, cultured in vitro with high-dose interleukin-2 (lL-2), further selected based on antigen specificity and tumor reactivity, and the selected TILs are subsequently expanded. Upon re-introduction of lifileucel into the patient, the TILs re-infiltrate the tumor, specifically recognize the tumor-associated antigens (TAAs), and initiate tumor cell lysis. IL-2 induces the proliferation and expansion of TILs in vitro.
  • Lifirafenib - An inhibitor of the serine/threonine protein kinase B-raf (BRAF) and epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Lifirafenib selectively binds to and inhibits the activity of BRAF and certain BRAF mutant forms, and EGFR. This prevents BRAF- and EGFR-mediated signaling and inhibits the proliferation of tumor cells that either contain a mutated BRAF gene or express over-activated EGFR. In addition, BGB-283 inhibits mutant forms of the Ras proteins K-RAS and N-RAS. BRAF and EGFR are mutated or upregulated in many tumor cell types.
  • Light-activated au-011 - A formulation composed of nanoparticles derived from the human papillomavirus (HPV-NPs) and conjugated to the infrared (IR)-activated fluorescent dye IR700 (IR-700), with potential antineoplastic activity. Upon intravitreal injection, the HPV-NPs target and bind to heparan-sulfated proteoglycans (HSPG) expressed by ocular melanoma cells. Upon irradiation with near-IR (NIR) light, the photosensitizer IR700 becomes activated, generates reactive oxygen species (ROS) and selectively damages the melanoma cell membrane, which induces necrosis of the melanoma cells while sparing the surrounding, healthy non-HSPG-expressing tissue, and potentially preserving vision. HSPGs are overexpressed on a variety of cancer cell types.
  • Lilotomab - A murine immunoglobulin G1 (IgG1) monoclonal antibody directed against the CD37 antigen with potential antineoplastic activity. Upon administration, lilotomab both activates the immune system to induce an antibody-dependent cell-mediated cytotoxicity (ADCC) against CD37-overexpressing tumor cells and induces apoptosis in these tumor cells. CD37 is a transmembrane glycoprotein expressed at high-levels on B-cells and to a lesser extent on T-cells and myeloid cells, and is frequently overexpressed in certain B-cell malignancies.
  • Limonene, (+)- - An oral dietary supplement containing a natural cyclic monoterpene and major component of the oil extracted from citrus peels with potential chemopreventive and antitumor activities. Although the mechanism of action has yet to be fully elucidated, limonene and its metabolites perillic acid, dihydroperillic acid, uroterpenol and limonene 1,2-diol may inhibit tumor growth through inhibition of p21-dependent signaling and may induce apoptosis via the induction of the transforming growth factor beta-signaling pathway. In addition, they inhibit post-translational modification of signal transduction proteins, resulting in G1 cell cycle arrest as well as differential expression of cell cycle- and apoptosis-related genes.
  • Limonene, (+/-)- - A racemic mixture of limonene, a natural cyclic monoterpene and major component of the oil extracted from citrus rind with chemo-preventive and antitumor activities. The metabolites of DL-limonene, perillic acid, dihydroperillic acid, uroterpenol and limonene 1,2-diol are suggested to inhibit tumor growth through inhibition of p21-dependent signaling, induce apoptosis via the induction of the transforming growth factor beta-signaling pathway, inhibit post-translational modification of signal transduction proteins, result in G1 cell cycle arrest as well as cause differential expression of cell cycle- and apoptosis-related genes.
  • Linifanib - An orally bioavailable receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Linifanib inhibits members of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor families; it exhibits much less activity against unrelated RTKs, soluble tyrosine kinases, or serine/threonine kinases. This agent does not have a general antiproliferative effect due to its high dose requirement. However, linifanib may exhibit potent antiproliferative and apoptotic effects on tumor cells whose proliferation is dependent on mutant kinases, such as FMS-related tyrosine kinase receptor-3 (FLT3).
  • Linoleyl carbonate-paclitaxel - A formulation of the 6-omega fatty acid derivative 2'-linoleyl carbonate (LOC) conjugated to paclitaxel, a taxane compound extracted from the Pacific yew tree Taxus brevifolia, with potential antineoplastic activity. Paclitaxel binds to and stabilizes tubulin, thereby interfering with the dynamics of microtubule assembly/disassembly and resulting in the inhibition of cell division. LOC enhances the uptake of paclitaxel by tumor cells, thereby concentrating this agent in tumor cells compared to normal cells, and may decrease its toxicity profile; fatty acids serve as energy sources and biochemical precursors for the fast growing tumor cells.
  • Linperlisib - An orally available selective inhibitor of the delta form of phosphatidylinositol 3-kinase (PI3-kinase subunit delta; PI3K-delta; PI3Kdelta), with potential antineoplastic activity. Upon oral administration linperlisib selectively binds to and inhibits PI3K-delta and prevents the activation of the PI3K/AKT signaling pathway. This decreases proliferation of and induces cell death in PI3K-delta over-expressing tumor cells. PI3K-delta also plays a key role in the B-cell receptor (BCR) signaling pathway and the proliferation of certain hematologic cancer cells. The targeted inhibition of PI3K-delta is designed to preserve PI3K signaling in normal, non-neoplastic cells, thereby minimizing serious side effects.
  • Linrodostat - An orally available inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), with potential immunomodulating and antineoplastic activities. Upon administration, linrodostat specifically targets and binds to IDO1, a cytosolic enzyme responsible for the oxidation of the amino acid tryptophan into the immunosuppressive metabolite kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, BMS-986205 restores and promotes the proliferation and activation of various immune cells, including dendritic cells (DCs), natural killer (NK) cells, and T-lymphocytes, and causes a reduction in tumor-associated regulatory T-cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may induce a cytotoxic T-lymphocyte (CTL) response against the IDO1-expressing tumor cells, thereby inhibiting the growth of IDO1-expressing tumor cells. IDO1, overexpressed by multiple tumor cell types, plays an important role in immunosuppression. Tryptophan depletion inhibits T-lymphocyte proliferation and activation, and subsequently suppresses the immune system.
  • Linsitinib - An orally bioavailable small molecule inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. Linsitinib selectively inhibits IGF-1R, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Overexpressed in a variety of human cancers, IGF-1R stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis.
  • Lintuzumab - A humanized recombinant monoclonal antibody directed against CD33, a cell surface antigen found on myeloid leukemia blasts and early hematopoietic progenitor cells. Lintuzumab stimulates antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells expressing CD33, resulting in a decrease in tumor burden. The humanized version of this monoclonal antibody exhibits less immunogenicity and improved binding affinity compared to its murine counterpart.
  • Liothyronine i-131 - A radioconjugate of synthetic active thyroid hormone, liothyronine (T3), labeled with Iodine 131. Liothyronine involves many important metabolic functions and is essential to the proper development and differentiation of all cells. I131 liothyronine may be used in radiotherapy in thyroid cancers.
  • Lipid encapsulated anti-plk1 sirna tkm-plk1 - short interfering RNAs (siRNAs) directed against polo-like kinase 1 (PLK1, STPK13), with potential antineoplastic activity. Upon administration of lipid-encapsulated anti-PLK1 siRNA TKM-PLK1, siRNA binds to PLK1 mRNA, which results in the inhibition of both the translation and expression of the PLK1 protein. Blockage of PLK1 expression prevents proper tumor cell mitosis, causes cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of PLK1-overexpressing tumor cells. PLK1, named after the polo gene of Drosophila melanogaster, is a serine/threonine kinase crucial in the regulation of mitosis; its expression is upregulated in a variety of tumor cell types and plays a key role in tumor cell proliferation. The pegylated lipid bilayer of SNALP provides stability and protects siRNA degradation; it facilitates uptake into the cell and release from endosomes.
  • Lipid nanoparticle encapsulated mrnas encoding human il-12a/il-12b medi-1191 - A formulation consisting of lipid nanoparticle encapsulated messenger RNA (mRNA) encoding human interleukin-12 subunit beta (IL-12B; IL-12 subunit p40) and interleukin-12 subunit alpha (IL-12A; IL-12 subunit p35) with potential immunomodulatory and antineoplastic activities. Although the exact mechanism of action has not been completely characterized, upon intratumoral injection, the lipid nanoparticle moiety presumably binds to the plasma membrane of nearby cells and releases the IL-12A and IL-12B mRNA into the cell. The mRNA is then translated by the cellular protein translation machinery to produce a single-chain fusion protein of IL-12B and IL-12A subunits, which is secreted into the local tumor microenvironment (TME). Secretion of IL-12 activates the immune system by promoting the secretion of interferon-gamma, activating natural killer cells (NKs), and inducing cytotoxic T-cell responses, which may result in both decreased tumor cell proliferation and enhanced immune-mediated destruction of tumor cells.
  • Lipid nanoparticle encapsulated ox40l mrna-2416 - A proprietary formulation consisting of a lipid nanoparticle encapsulating a synthetic messenger RNA (mRNA) encoding the human co-stimulatory protein tumor necrosis factor ligand superfamily member 4 (TNFSF4; OX40 Ligand; OX40L), with potential immunomodulatory and antitumor activities. Although the mechanism of action has not been completely characterized, following intratumoral injection of lipid nanoparticle encapsulated OX40L mRNA-2416, the lipid nanoparticle moiety presumably binds to the plasma membrane of nearby cells and releases the OX40L mRNA into the cell. The OX40L mRNA is then translated by the cellular protein translation machinery to produce OX40L protein, which is then expressed on the plasma membrane of the cells that internalized the OX40L mRNA. OX40L binds to and activates signaling pathways downstream of its cognate receptor tumor necrosis factor receptor superfamily member 4 (TNFRSF4; OX40), which is expressed on activated T-cells. OX40L/OX40 binding promotes increased cytokine production, which can induce proliferation of memory and effector T-lymphocytes. Altogether, this may enhance an immune response that promotes the killing of nearby tumor cells. OX40L, a cell surface glycoprotein and member of the tumor necrosis factor (TNF) ligand family, provides a co-stimulatory signal for the proliferation and survival of activated T cells.
  • Lipid nanoparticle encapsulating glutathione s-transferase p sirna nbf-006 - A biodegradable, lyophilized lipid nanoparticle (LNP) encapsulating small interfering ribonucleic acid (siRNA) directed against glutathione S-transferase P (GSTP), with potential antineoplastic activity. Upon administration of LNP encapsulating GSTP siRNA NBF-006, the LNP formulation delivers the siRNA particles to the tumor cells where the GSTP siRNA targets and binds to GSTP mRNA. This results in the inhibition of the translation and expression of GSTP and may inhibit proliferation of KRAS-overexpressing tumor cells. GSTP, an enzyme overexpressed in many tumor cell types, is involved in modulating MAP kinase-related cell-signaling pathways.
  • Lipid nanoparticle encapsulating mrnas encoding human ox40l/il-23/il-36gamma mrna-2752 - A lipid nanoparticle encapsulating mRNAs encoding for the human co-stimulatory protein tumor necrosis factor ligand superfamily member 4 (TNFSF4; OX40 Ligand; OX40L), the pro-inflammatory cytokines interleukin-23 (IL-23) and interleukin-36gamma (IL-36gamma), with potential immunomodulatory and anti-tumor activities. Upon intratumoral (IT) injection of the lipid nanoparticle encapsulated mRNAs encoding human OX40L/IL-23/IL-36gamma mRNA-2752, the lipid nanoparticle binds to the plasma membrane of cells and releases the mRNAs into the cell. The OX40L mRNA is then translated by the cellular protein translation machinery to produce OX40L protein, which is then expressed on the plasma membrane of the cells that internalized the OX40L mRNA. OX40L binds to and activates signaling pathways downstream of its cognate receptor tumor necrosis factor receptor superfamily member 4 (TNFRSF4; OX40), which is expressed on activated T-cells. OX40L/OX40 binding promotes increased cytokine production, which can induce proliferation of memory and effector T-lymphocytes against the nearby tumor cells. The co-administration of IL-23 and IL-36gamma further stimulates anti-tumor immune responses. Altogether, this may enhance T-cell mediated anti-tumor immune responses thereby killing of the tumor cells. OX40L, a cell surface glycoprotein and member of the tumor necrosis factor (TNF) ligand superfamily, provides a co-stimulatory signal for the proliferation and survival of activated T-cells. IL-36gamma activates innate immune cells and promotes T-helper 1 (Th1) responses, whereas IL-23 has been implicated in Th1/Th17 immunity as well as in the modulation of antigen-presenting cells (APCs).
  • Liposomal bcl-2 antisense oligonucleotide bp1002 - A liposomal-based nanoparticle composed of an uncharged P-ethoxy antisense oligodeoxynucleotide (ODN) targeting Bcl-2 mRNA and incorporated in liposomes, with potential antineoplastic activity. Upon administration of liposomal Bcl-2 antisense oligonucleotide BP1002, this agent targets and hybridizes with Bcl-2 mRNA and inhibits the expression of Bcl-2 protein. This may induce tumor cell apoptosis of Bcl2-overexpressing tumor cells and may decrease tumor cell proliferation. Bcl2, a protein involved in regulating programmed cell death, is overexpressed in a wide variety of tumors. It promotes cellular survival and inhibits apoptosis.
  • Liposomal c-raf antisense oligonucleotide - The liposomal formulation of a c-raf-1 antisense oligonucleotide, with potential antineoplastic activity. Liposomal c-raf antisense oligonucleotide targets the translation initiation site of human c-raf-1 mRNA, thereby blocking the expression and production of Raf-1 protein and thus inhibit tumor cell growth and development. Raf-1 plays a key role in the RAF/MEK/ERK signaling pathway, which regulates mammalian cell proliferation and growth. The liposomal formulation increases the solubility of the c-raf antisense oligonucleotide, thus improving its pharmacodynamic profile.
  • Liposomal curcumin - A liposomal formulation containing curcumin, a poorly water-soluble polylphenol pigment isolated from the plant Curcuma longa, with potential antineoplastic, chemopreventive, antioxidant, anti-angiogenic and anti-inflammatory activities. Upon intravenous administration of liposomal curcumin, this agent blocks the formation of reactive-oxygen species, neutralizes free radicals, and exhibits anti-inflammatory properties as a result of inhibition of cyclooxygenases (COX) and other enzymes involved in inflammation. In addition, curcumin disrupts various cell signal transduction pathways involved in carcinogenesis, inhibits the activity of nuclear factor-kappa B (NF-kB), SRC, and annexin A2 (ANXA2), and reduces the expression of both matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor receptor 2 (VEGFR2). This prevents and/or inhibits tumor cell formation and proliferation. Liposome encapsulation of curcumin improves its efficacy, when compared to the administration of unencapsulated curcumin.
  • Liposomal cytarabine - A liposomal intrathecal formulation of the antimetabolite cytarabine. As an S-phase-specific antimetabolite, cytarabine is phosphorylated by deoxycytidine kinase to a triphosphate form which competes with thymidine for incorporation into DNA; the incorporation of cytarabine triphosphate into DNA appears to inhibit DNA polymerase and so DNA synthesis, resulting in cell death.
  • Liposomal daunorubicin citrate - A liposome-encapsulated form of the citrate salt of the anthracycline antineoplastic antibiotic daunorubicin. Daunorubicin intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. Liposomal delivery of doxorubicin citrate improves drug penetration into tumors and decreases drug clearance, thereby increasing the duration of therapeutic drug effects.
  • Liposomal docetaxel - A formulation of the poorly soluble, semi-synthetic, second-generation taxane docetaxel encapsulated within liposomes, with antineoplastic activity. Upon intravenous administration, docetaxel binds to and stabilizes tubulin, thereby inhibiting microtubule disassembly which results in cell-cycle arrest at the G2/M phase and cell death. This liposomal formulation solubilizes docetaxel without the use of toxic solvents such as Tween 80, permitting the administration of larger doses of docetaxel while avoiding solvent-associated toxicity, including hypersensitivity reactions. In addition, liposomal delivery of docetaxel improves drug penetration into tumors and decreases drug clearance, thereby increasing the duration of therapeutic drug effects while lowering the toxicity profile.
  • Liposomal eribulin mesylate - A liposome-encapsulated formulation of the mesylate salt form of eribulin, a synthetic, macrocyclic ketone analogue of halichondrin B, a substance derived from the marine sponge genus Halichondria, with potential antineoplastic activity. Eribulin binds to the vinca domain of tubulin and inhibits both the polymerization of tubulin and the assembly of microtubules. This results in the inhibition of mitotic spindle assembly, the induction of cell cycle arrest at G2/M phase, as well as tumor cell apoptosis. Compared to the administration of eribulin alone, liposomal delivery of eribulin allows for a longer half-life, which allows increased drug concentration in target tissues while decreasing systemic toxicity.
  • Liposomal hpv-16 e6/e7 multipeptide vaccine pds0101 - A liposomal nanoparticle-based therapeutic vaccine composed of the cationic lipid R-DOTAP (R-enantiomer of 1,2-dioleoyl-3-trimethylammonium-propane chloride) encapsulating six human papillomavirus 16 (HPV-16) E6 and E7 peptides, with potential immunostimulating activity. Upon subcutaneous administration of the liposomal HPV-16 E6 and E7 multipeptide vaccine, the nanoparticles are taken up by antigen presenting cells (APCs), specifically dendritic cells (DCs), which may stimulate the immune system to induce a cytotoxic T-lymphocyte response (CTL) against HPV-16 E6 and E7-expressing tumor cells. HPV-16 E6 and E7 are oncoproteins that play a key role in the tumorigenesis of a variety of cancers.
  • Liposomal mitoxantrone hydrochloride - A formulation composed of the hydrochloride salt form of the anthracenedione antibiotic mitoxantrone encapsulated within liposomes, with potential antineoplastic activity. Upon intravenous administration, mitoxantrone intercalates into and forms crosslinks with DNA, thereby disrupting DNA and RNA replication. This agent also binds to topoisomerase II, which both results in DNA strand breaks and prevents DNA synthesis. This leads to the induction of apoptosis in the rapidly dividing cancer cells. The liposomal delivery of mitoxantrone improves drug penetration into tumors and decreases drug clearance, thereby increasing drug circulation and therapeutic efficacy while lowering the toxic effects.
  • Liposomal muc1/pet-lipid a vaccine ont-10 - A cancer vaccine comprised of a 43 amino acid epitope from glycoprotein MUC1 (mucin 1) and the synthetic Toll-like receptor 4 (TLR-4) agonist PET lipid A encapsulated in cholesterol/dipalmitoylphosphatidylcholine (DPPC)/dimyristoylphosphatidylglycerol (DMPG) liposomes, with potential immunostimulatory and antineoplastic activities. The MUC1 epitope is composed of two 20 amino glycosylated VNTR (various number tandem repeats) from human MUC1A and including 6 glycosylated sites modified by Tn (alfa-N-acetyl-D-galactosamine). Immunization of liposomal MUC1/PET-lipid A vaccine ONT-10 results in an antibody as well as a cytotoxic T-lymphocyte (CTL) response against hypoglycosylated MUC1 expressing tumor cells. The tumor associated antigen MUC1, a type I transmembrane protein, is overexpressed and aberrantly glycosylated in a variety of tumor cells. As a vaccine adjuvant, PET lipid A, also known as penta erythritol lipid A, stimulates both cellular and humoral responses to the vaccine antigen.
  • Liposomal nddp - A synthetic liposomal formulation of bis-neodecanoate diaminocyclohexane platinum (NDDP), a third-generation platinum complex analogue of cisplatin, with potential antineoplastic activity. After displacement of the 2 long-chain aliphatic leaving groups (neodecanoic acid), platinum diaminocyclohexane (DACH) complexes become highly reactive and alkylate macromolecules, forming both inter- and intra-stranded DNA cross-linkings and inhibiting DNA synthesis, which results in tumor cell cytotoxicity. Because DNA mismatch-repair (MMR) complexes do not recognize DACH-platinum adducts, DNA repair mechanisms are inhibited, overcoming limitations observed with other platinum-based agents. In addition, the liposomal encapsulation improves the bioavailability of NDDP and reduces its toxicity profile.
  • Liposomal rhenium re 186 - A therapeutic preparation consisting of the beta-emitting radioisotope rhenium Re 186 encapsulated in a nanoliposome, with potential antineoplastic activity. Upon intratumoral infusion of liposomal rhenium Re 186, the radioisotope releases radiation, which directly kills the tumor cells. The nanoliposomes facilitate the retention of the radioisotope by the tumor cells and localize the radiocytotoxicity to the tumor while sparing surrounding normal, healthy cells. Re-186 has a short half-life and a short path length, which contributes further to limiting the radiotoxicity to the tumor cells.
  • Liposomal sn-38 - The liposomal formulation of SN-38 (7-ethyl-10-hydroxy-camptothecin), a biologically active metabolite of the prodrug irinotecan, with potential antineoplastic activity. SN-38 binds to and inhibits topoisomerase I by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks, inhibition of DNA replication, and apoptosis. SN-38 has been reported to exhibit up to 1,000-fold more cytotoxic activity against various cancer cells in vitro than irinotecan. The liposomal formulation of SN-38 increases the solubility of SN-38, which is a relatively insoluble compound, and improves the pharmacodynamic profile as compared to SN-38 alone.
  • Liposomal topotecan ff-10850 - A liposome encapsulated formulation of the semisynthetic camptothecin analogue topotecan with potential antineoplastic activity. Upon administration, liposomal topotecan FF-10850 preferentially releases topotecan, a cytotoxic, quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminate, into the tumor environment. Topotecan inhibits topoisomerase I activity by stabilizing the topoisomerase I-DNA covalent complexes during S phase of the cell cycle, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery. The novel liposome used in this agent prolongs its serum half-life while promoting efficient drug delivery into the cytosol from the endosome compartment of the tumor cell, which may minimize the adverse effect of bone marrow suppression.
  • Liposomal vinorelbine - A formulation of the semisynthetic vinca alkaloid, vinorelbine, encapsulated within liposomes, with antineoplastic activity. Vinorelbine binds to tubulin and prevents formation of the mitotic spindle, resulting in cell cycle arrest in metaphase. Like other vinca alkaloids, vinorelbine may also interfere with the metabolism of nucleic acids, lipids, amino acids, cAMP, and glutathione, as well as other biological processes including calmodulin-dependent Ca2+-transport, ATPase activity, or cellular respiration. Liposomal delivery of vinorelbine improves drug penetration into tumors and decreases drug clearance, thereby increasing the duration of therapeutic effects while lowering the toxicity profile.
  • Liposomal-based cream base - A smooth, thick cream that is used as a base for topical and transdermal delivery of pharmaceuticals. The proprietary formula utilizes a multi-emulsion liposomic system that is insoluble in water and alcohol.
  • Liposome-encapsulated daunorubicin-cytarabine - A liposomal formulation containing a fixed combination of the antineoplastic agents cytarabine and daunorubicin in a 5:1 molar ratio. Liposome-encapsulated daunorubicin-cytarabine has been designed to provide optimal delivery of a specific ratio of cytarabine to daunorubicin, one that has been shown to be synergistic in vitro. The antimetabolite cytarabine competes with cytidine for incorporation into DNA, inhibiting DNA synthesis. This agent also inhibits DNA polymerase, resulting in a decrease in DNA replication and repair. Daunorubicin, an intercalator and a topoisomerase II inhibitor, prevents DNA replication and inhibits protein synthesis. This agent also generates oxygen free radicals, resulting in the cytotoxic lipid peroxidation of cell membrane lipids.
  • Liposome-encapsulated doxorubicin citrate - A formulation of the citrate salt of the antineoplastic anthracycline antibiotic doxorubicin, encapsulated within liposomes, with antitumor activity. Doxorubicin intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and RNA synthesis. This agent also interacts with cell membrane lipids causing lipid peroxidation. Liposomal delivery of doxorubicin improves drug penetration into tumors and decreases drug clearance, thereby increasing the duration of therapeutic drug effects while lowering the toxicity profile.
  • Liposome-encapsulated mir-34 mimic mrx34 - A liposomal formulation containing a nucleotide that mimics the human tumor suppressor microRNA (miRNA) miR-34, with potential antineoplastic activity. Upon administration, liposome-encapsulated MRX34 mimics miR-34 by inhibiting the expression of a variety of oncogenes including MYC, MET, BCL2, and beta-catenin. This induces cell cycle arrest, senescence and apoptosis in susceptible tumor cells. miR-34 is downregulated in most solid and hematologic malignancies and regulates the expression of a variety of genes. This miRNA plays an important role in the inhibition of cancer cell stemness, metastasis and cancer cell survival.
  • Liposome-encapsulated osi-7904 - A liposome-encapsulated formulation of the benzoquinazoline folate analog OSI-7904 with antineoplastic activity. As a thymidylate synthase inhibitor, OSI-7904 noncompetitively binds to thymidylate synthase, resulting in inhibition of thymine nucleotide synthesis and DNA replication. Liposome encapsulation improves the efficacy and increases the half-life of OSI-7904.
  • Liposome-encapsulated rb94 plasmid dna gene therapy agent sgt-94 - A systemic gene therapy anti-cancer agent composed of cationic liposomes, which encapsulates plasmid DNA encoding for the tumor suppressor gene RB94 and is complexed with anti-transferrin receptor single chain antibody fragment (TfRscFv), with potential antineoplastic activity. Upon systemic administration of liposome-encapsulated RB94 plasmid DNA gene therapy agent SGT-94, the TfRscFv portion of this agent selectively targets the tumor cells expressing transferrin receptors. TfRscFv binding to the transferrin receptor allows receptor-mediated endocytosis and transfection, followed by the expression of RB94 gene. This induces tumor cell apoptosis through an as of yet unknown pathway. RB94 is a modified, N-terminal truncated form of the full-length protein retinoblastoma gene RB110, and exerts enhanced antitumor activity. The transferrin receptor (TfR) functions in cellular iron uptake through its interaction with transferrin, and is overexpressed in a variety of tumor types.
  • Liposome-encapsulated taas mrna vaccine w_ova1 - A vaccine consisting of messenger RNA (mRNA) encoding three tumor-associated antigens (TAAs) specific for ovarian cancer that are encapsulated in liposomes, with potential immunomodulating and antineoplastic activities. Upon administration of the liposome-encapsulated TAAs mRNA vaccine W_ova1, the liposomes bind to the plasma membrane of cells and release the mRNA into the cells. The mRNA is then translated by ribosomes to produce the TAAs. The TAAs are presented to the immune system which may activate both humoral and cellular immune responses against the ovarian cancer cells expressing these TAAs.
  • Lirilumab - A fully human monoclonal antibody against killer-cell immunoglobulin-like receptors (KIR), with potential antineoplastic activity. Upon administration, lirilumab binds to KIR, thereby preventing the binding of KIR ligands to KIR on natural killer (NK) cells. By blocking these inhibitory receptors, NK cells become activated and attack cancer cells leading to tumor cell death. KIR, a member of the immunoglobulin superfamily, is expressed on the surface of NK cells.
  • Lisavanbulin - An orally available, highly water-soluble lysine prodrug of the synthetic small molecule BAL27862 with potential antitumor activity. Upon administration of lisavanbulin and conversion into the active form BAL27862, this agent binds to tubulin at a site distinct from the vinca-alkaloid-binding site, and prevents tubulin polymerization and destabilizes microtubules, ultimately leading to cell cycle arrest, blockage of cell division and an induction of cell death in cancer cells.
  • Lisocabtagene maraleucel - A preparation of a defined ratio of CD4+ and CD8+ autologous T-lymphocytes transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) containing an anti-CD19 single chain variable fragment (scFv) fused to the signaling domain of 4-1BB (CD137), the zeta chain of the TCR/CD3 complex (CD3-zeta), and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, lisocabtagene maraleucel is directed to and induces selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) response. The 4-1BB costimulatory signaling domain enhances both proliferation of T-cells and antitumor activity.
  • Listeria monocytogenes-llo-psa vaccine adxs31-142 - A cancer vaccine containing a live-attenuated strain of the Gram-positive bacterium Listeria monocytogenes (Lm) encoding a fusion protein composed of the tumor-associated antigen (TAA) human prostate-specific antigen (PSA) fused to a fragment of the immunostimulant listeriolysin O (LLO) protein, with potential immunostimulatory and antineoplastic activities. Upon administration of the Lm-LLO-PSA vaccine ADXS31-142, the expressed LLO-PSA is processed by antigen presenting cells (APCs), presented to the immune system by both major histocompatibility complex (MHC) I and II molecules, and activates the immune system to exert both an innate and adaptive immune response involving the recruitment and activation of T-lymphocytes against PSA-expressing tumor cells as well as the inhibition of tumor-infiltrating T regulatory cells (T regs) and myeloid-derived suppressor cells (MDSCs). This eventually results in tumor cell lysis.
  • Litronesib - An inhibitor of the kinesin-related motor protein Eg5 with potential antineoplastic activity. Litronesib selectively inhibits the activity of Eg5, which may result in mitotic disruption, apoptosis and consequently cell death in tumor cells that are actively dividing. The ATP-dependent Eg5 kinesin-related motor protein (also known as KIF11 or kinesin spindle protein-5) is a plus-end directed kinesin motor protein that plays an essential role during mitosis, particularly in the regulation of spindle dynamics, including assembly and maintenance.
  • Live attenuated measles virus vaccine - A live, attenuated measles vaccine with potential antineoplastic activity. Upon subcutaneous administration, live attenuated measles virus vaccine may activate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against measles-positive tumor cells. Measles virus has been shown to be present in some non-small cell lung cancers.
  • Live freeze-dried lactic acid bacteria probiotic - A probiotic containing live, cultivated, freeze-dried lactic acid bacteria with gastrointestinal (GI) protective, anti-inflammatory, immunomodulating and potential antitumor properties. Oral administration of probiotic bacteria help maintain adequate colonization of the GI tract and modulate the composition of the normal microflora. Upon colonization of the GI tract, the probiotic bacteria form a protective barrier, interfere with the attachment of pathogenic bacteria and other harmful substances and may bind to and degrade carcinogens. This may prevent inflammation and possibly cancer. In addition, these bacteria produce lactic acid, thereby creating an acidic environment that is unfavorable for pathogens.
  • Live-attenuated listeria encoding human mesothelin vaccine crs-207 - A recombinant Listeria-based cancer vaccine containing a live-attenuated strain of the facultative intracellular bacterium Listeria monocytogenes (Lm) expressing human mesothelin with potential immunostimulatory and antineoplastic activities. Upon administration of this vaccine, Listeria invade professional phagocytes within the immune system and express mesothelin, which may activate a cytotoxic T-lymphocyte (CTL) response against mesothelin-expressing tumor cells, resulting in tumor cell lysis. In addition, the Listeria vector itself may induce a potent innate and adaptive immunity unrelated to mesothelin expression. Mesothelin is a cell surface glycoprotein involved in cell adhesion and is overexpressed in many epithelial-derived cancers, including pancreatic, ovarian and lung cancers, and malignant mesotheliomas.
  • Live-attenuated listeria monocytogenes-encoding egfrviii-ny-eso-1 vaccine adu-623 - A live-attenuated, double-deleted strain of the Gram-positive bacterium Listeria monocytogenes (Lm) encoding a mutant form of the tumor associated antigens, epidermal growth factor receptor (EGFRvIII) and the cancer/testis antigen NY-ESO-1, with potential immunostimulatory and antineoplastic activities. Upon intravenous administration, live-attenuated Listeria monocytogenes encoding EGFRvIII-NY-ESO-1 vaccine targets dendritic cells and expresses EGFRvIII and NY-ESO-1. This promotes both a potent innate immune response and an adaptive immune response involving the recruitment and activation of T lymphocytes against EGFRvIII and NY-ESO-1-expressing tumor cells, which results in tumor cell lysis.
  • Liver x receptor beta agonist rgx-104 - An orally bioavailable agonist of the nuclear receptor liver X receptor beta (LXRbeta; NR1H2; LXR-b), with potential immunomodulating and antineoplastic activities. Upon oral administration, LXRbeta agonist RGX-104 selectively targets and binds to LXRbeta, thereby activating LXRbeta-mediated signaling, leading to the transcription of certain tumor suppressor genes and the downregulation of certain tumor promoter genes. This particularly activates the expression of apolipoprotein E (ApoE), a tumor suppressor protein, in tumor cells and certain immune cells. This activates the innate immune system, resulting in depletion of immunosuppressive myeloid-derived suppressor cells (MDSCs), tumor cells and endothelial cells in the tumor microenvironment. This reverses immune evasion, enhances anti-tumor immune responses and inhibits proliferation of tumor cells. LXRbeta, a member of the oxysterol receptor family, which is in the nuclear receptor family of transcription factors, plays a key role in cholesterol transport, glucose metabolism and the modulation of inflammatory responses; activation of LXRbeta suppresses tumor cell invasion, angiogenesis, tumor progression, and metastasis in a variety of tumor cell types. The expression of the ApoE protein becomes silenced in human cancers as they grow, become invasive, and metastasize; ApoE silencing is related to reduced survival in cancer patients. The LXR-ApoE pathway regulates the ability of cancers to evade the immune system and recruit blood vessels.
  • L-lysine/l-arginine-containing amino acid - An intravenous (IV) amino acid (AA) solution containing the cationic amino acids L-lysine and L-arginine, with radioprotective activity. Upon IV administration of the AA solution, L-lysine and L-arginine are specifically taken up by the kidneys. This protects the kidneys from toxicity by certain co-administered radio-labeled peptides as they compete with radio-labeled peptides for renal uptake. This reduces uptake of the radio-labeled peptides by the kidneys and decreases their renal retention. It also increases the target-to-kidney ratio of the radio-labeled peptides, thereby reducing radiation exposure to the kidneys and preventing nephrotoxicity.
  • Lmb-1 immunotoxin - A chimeric protein consisting of the Fv portion of a monoclonal antibody attached to a fragment of Pseudomonas exotoxin A without its cell-binding region. LMB-1 immunotoxin targets B3, a Lewis Y-related carbohydrate epitope found on some solid tumors. The antibody attaches to the tumor cell and the exotoxin stops protein synthesis by inactivating elongation factor 2.
  • Lmb-2 immunotoxin - A fusion protein consisting of the Fv portion of a monoclonal antibody attached to a 38-kDa fragment of the Pseudomonas exotoxin A (with amino acids 365-380 deleted). LMB-2 immunotoxin targets the interleukin 2 receptor (also known as IL-2R or CD25) which is expressed on activated normal T and B cells and macrophages and on the cells of various hematologic malignancies. The antibody attaches to the IL-2R on the cell membrane, facilitating the entry of the exotoxin. The exotoxin moiety induces caspase-mediated apoptosis of tumor cells via a mechanism involving mitochondrial damage; it also catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, thereby inactivating elongation factor 2 and inhibiting protein synthesis.
  • Lmb-7 immunotoxin - A single chain chimeric protein consisting of a monoclonal antibody fragment attached to a portion of the Pseudomonas exotoxin A. LMB-7 immunotoxin attaches to B3, a Lewis Y-related carbohydrate epitope on some solid tumor cells. The antibody attaches to the cell and the exotoxin inhibits protein synthesis by inactivating elongation factor 2.
  • Lmb-9 immunotoxin - A recombinant disulfide stabilized anti-Lewis Y IgG immunotoxin containing a 38 KD toxic element derived from the Pseudomonas aeruginosa exotoxin A and a monoclonal antibody fragment, designed to target adenocarcinomas expressing Lewis Y. LMB-9 immunotoxin attaches to tumor cells, facilitating he entry of the exotoxin. The exotoxin moiety induces caspase-mediated apoptosis of tumor cells via a mechanism involving mitochondrial damage; it also catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, thereby inactivating elongation factor 2 and inhibiting protein synthesis.
  • Lmdda-llo-chher2 fusion protein-secreting live-attenuated listeria cancer vaccine adxs31-164 - A cancer vaccine containing a live, highly attenuated strain of the Gram-positive bacterium Listeria monocytogenes (LmddA) encoding a fusion protein composed of a chimeric peptide comprised of three highly immunogenic epitopes of the human tumor-associated antigen (TAA) HER2/neu (chHER2) fused to a non-hemolytic fragment of the immunostimulant listeriolysin O (LLO) protein, with potential immunostimulatory and antineoplastic activities. Upon administration of the LmddA-LLO-chHER2 vaccine ADXS31-142, the LmddA is taken up by phagocytic cells; then the listeriolysin portion of the expressed LLO-chHER2 can form pores in the phagolysosomes and the fusion protein can escape into the cytosol. In turn, the LLO-chHER2 is processed and presented to the immune system by major histocompatibility complex (MHC) I on the phagocytic cells. Antigen presentation activates the immune system to exert an immune response involving the recruitment and activation of T-lymphocytes against HER2-expressing tumor cells, and inhibits tumor-infiltrating T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). This eventually results in tumor cell lysis. HER2/neu, a tyrosine kinase receptor belonging to the epidermal growth factor receptor (EGFR) family, is overexpressed in various tumor cell types.
  • L-methylfolate - A nutritional supplement containing the biologically active form of the B9 vitamin folate, 5-methyltetrahydrofolate (L-methylfolate), with potential antineoplastic activity. Upon administration, L-methylfolate is able to provide methyl groups allowing an increase in the level of DNA methylation in the promoter regions of certain tumor-promoting genes, thereby reversing the DNA hypomethylation of these genes and inactivating them. This may result in a decrease of both tumor cell proliferation and tumor progression. In addition, administration of L-methylfolate may sensitize tumor cells to the cytotoxic effects of other chemotherapeutic agents. Unlike folic acid, L-methylfolate is able to cross the blood brain barrier and could be beneficial in the treatment of brain tumors. DNA hypomethylation of certain genes leads to chromosome instability and contributes to tumor development.
  • Lmp1/barf1/ebna1-specific cytotoxic t-lymphocytes - A preparation of allogeneic cytotoxic T-lymphocytes (CTL) made specifically reactive to three Epstein-Barr virus (EBV) proteins, latent membrane protein (LMP) 1, BamH1-A rightward frame-1 (BARF1) and EBV nuclear antigen 1 (EBNA1), with potential antineoplastic activity. Administration of LMP1/BARF1/ EBNA1-specific CTLs to patients with LMP1/BARF1/EBNA1-positive tumors may result in a specific CTL response against the tumor cells expressing these antigens, which can result in both cell lysis and the inhibition of tumor cell proliferation. LMP1, BARF1 and EBNA1 are expressed in various, EBV-associated malignancies, including nasopharyngeal cancer and EBV-positive Hodgkin lymphoma.
  • Lmp-2:340-349 peptide vaccine - A peptide vaccine containing amino acids residues from 340 through 349 of the latent membrane protein-2 (LMP-2) of the Epstein-Barr virus (EBV) with potential immunostimulating and antineoplastic activities. LMP-2, an EBV transmembrane protein, is expressed in various malignancies including nasopharyngeal cancer and EBV-positive Hodgkin disease. Vaccination with the LMP-2:340-349 peptide may boost the immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against LMP-2 producing cells, resulting in cell lysis and inhibition of cancer cell proliferation.
  • Lmp-2:419-427 peptide vaccine - A peptide vaccine containing amino acids residues from 419 through 427 of the latent membrane protein-2 (LMP-2) of the Epstein-Barr virus (EBV) with potential immunostimulating and antineoplastic activities. LMP-2, an EBV transmembrane protein, is expressed in various malignancies including nasopharyngeal cancer and EBV-positive Hodgkin disease. Vaccination with the LMP-2:49-427 peptide may boost the immune system to mount a specific cytotoxic T-lymphocyte response against LMP-2 producing cells, resulting in cell lysis and inhibition of cancer cell proliferation.
  • Lmp2a-specific cytotoxic t-lymphocytes - A preparation of cytotoxic T-lymphocytes (CTL), specifically reactive to Epstein-Barr virus (EBV) latent membrane protein-2A (LMP2A), with potential antineoplastic activity. T-lymphocytes are exposed ex vivo to dendritic cells (DCs) transfected with a replication-deficient adenovirus encoding EBV LMP2A. Subsequently, LMP2A-specific CTLs are exposed to EBV infected cells transfected with adenovirus encoding LMP2A, thereby further stimulating CTLs. Administered to patients with EBV-positive tumors, LMP2A-specific CTLs target LMP2A-positive cells, resulting in cell lysis and inhibition of cancer cell proliferation. EBV LMP2A may be expressed in various malignancies, including nasopharyngeal carcinoma and Hodgkin and non-Hodgkin lymphomas.
  • Lmp2-specific t cell receptor-transduced autologous t-lymphocytes - A preparation of autologous T-lymphocytes that have been transduced with a lentiviral vector encoding a T-cell receptor (TCR) specific for human leukocyte antigen (HLA)-A02:01/24:02/11:01-restricted Epstein-Barr virus (EBV) latent membrane proteins (LMP) 1 and 2, and EBV nuclear antigen 1 (EBNA1), with potential antineoplastic activity. Upon administration, the autologous LMP1/LMP2/EBNA1-specific, HLA-A02:01/24:02/11:01-restricted TCR-expressing T-lymphocytes YT-E001 recognize and bind to HLA-presented EBV peptides, which may promote cell death and inhibit the growth of tumor cells expressing LMP1, LMP2 or EBNA1. LMP1, LMP2, and EBNA1 are expressed in various, EBV-associated malignancies, including nasopharyngeal cancer and EBV-positive Hodgkin lymphoma.
  • Lmp7 inhibitor m3258 - An orally bioavailable, potent, selective, reversible inhibitor of the large multifunctional peptidase 7 (LMP7, Beta5i, PSMB8), a chymotrypsin-like, proteolytic subunit of the immunoproteasome, with potential antineoplastic activity. Upon oral administration, LMP7 inhibitor M3258 targets and inhibits the proteolytic activity of the LMP7 subunit of immunoproteasome, thereby blocking its deubiquitylating activity. This blocks the ubiquitin proteasome degradation pathway, prevents the degradation of defective proteins, and leads to an accumulation of poly-ubiquitylated proteins. This induces the unfolded protein response (UPR) and results in both the induction of tumor cell apoptosis and the inhibition of tumor cell growth. Proteasomes are large multi-subunit protease complexes that degrade unneeded or damaged proteins that have been ubiquitinated, thereby restoring protein homeostasis. Unlike the constitutive proteasome, which is expressed in most tissues, immunoproteasome is specifically present in normal and malignant hematopoietic cells, including multiple myeloma. Immunoproteasome degrades ubiquitinated proteins, generates peptides for presentation on MHC class I, and plays a key role in the adaptive immune response and inflammatory diseases.
  • Lm-tllo-neoantigens vaccine adxs-neo - A proprietary, personalized plasmid DNA-based cancer vaccine composed of a live-attenuated strain of the Gram-positive bacterium Listeria monocytogenes (Lm) carrying a proprietary plasmid vector encoding multiple, patient-specific, immunogenic neoepitopes fused to a truncated form of the immunostimulant listeriolysin O (tLLO), with potential immunostimulatory and antineoplastic activities. Upon administration of the Lm-tLLO-neoantigens vaccine ADXS-NEO, the ADXS-NEO is taken up by antigen presenting cells (APCs), such as dendritic cells (DCs), and the expressed tLLO-neoantigens fusion protein is processed and presented to the immune system by both major histocompatibility complex (MHC) I and II molecules. This activates the immune system to exert both innate and adaptive immune responses involving the recruitment and activation of T-lymphocytes against the tumor-associated antigens (TAAs) specifically expressed by the patient's tumor cells, and inhibits the immunosuppressive tumor-infiltrating T-regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME). This results in tumor cell lysis. The various unique mutation-derived TAAs that are used in ADXS-NEO are identified from a biopsy of the patient's tumor.
  • Lobaplatin - A third-generation, water-soluble platinum compound with potential antineoplastic activity. Lobaplatin forms highly reactive, charged, platinum complexes that bind to nucleophilic groups such as GC- and AG-rich sites in DNA, inducing intrastrand DNA cross-links. These cross-links will ultimately result in induction of apoptosis and cell growth inhibition. Compared to first and second generation platinum compounds, lobaplatin appears to be more stable, less toxic, have a better therapeutic index and may overcome tumor resistance.
  • Lodapolimab - A monoclonal antibody directed against programmed cell death-1 ligand 1 (PD-L1) with immune checkpoint inhibitory and potential antineoplastic activities. Upon administration, lodapolimab binds to PD-L1 and prevents the interaction of PD-L1 with its receptor programmed cell death protein 1 (PD-1). This inhibits the activation of PD-1 and its downstream signaling pathways, which may enhance the T-cell-mediated immune response to neoplasms and reverse T-cell inactivation. PD-L1 is overexpressed by many human cancer cell types. PD-L1 binding to PD-1 on T-cells suppresses the immune system and results in immune evasion. PD-1, a transmembrane protein expressed on activated T-cells, is a negative regulator of the immune system that limits the expansion and survival of CD8+ T-cells.
  • Lometrexol - A folate analog antimetabolite with antineoplastic activity. As the 6R diastereomer of 5,10-dideazatetrahydrofolate, lometrexol inhibits glycinamide ribonucleotide formyltransferase (GARFT), the enzyme that catalyzes the first step in the de novo purine biosynthetic pathway, thereby inhibiting DNA synthesis, arresting cells in the S phase of the cell cycle, and inhibiting tumor cell proliferation. The agent has been shown to be active against tumors that are resistant to the folate antagonist methotrexate.
  • Lometrexol sodium - The sodium salt form of lometrexol, a folate analogue antimetabolite with antineoplastic activity. As the stereoisomer of 5,10-dideazatetrahydrofolate, lometrexol selectively inhibits glycinamide ribonucleotide formyltransferase (GARFT), the enzyme that catalyzes the first step in the de novo purine biosynthetic pathway, thereby inhibiting DNA synthesis and leading to an inhibition of tumor cell proliferation. The agent has been shown to be active against tumors that are resistant to the folate antagonist methotrexate, but causes severe, dose-limiting toxicities.
  • Lomustine - A nitrosourea with antineoplastic activity. Lomustine alkylates and crosslinks DNA, thereby inhibiting DNA and RNA synthesis. This agent also carbamoylates DNA and proteins, resulting in inhibition of DNA and RNA synthesis and disruption of RNA processing. Lomustine is lipophilic and crosses the blood-brain barrier.
  • Lonafarnib - A synthetic tricyclic derivative of carboxamide with antineoplastic properties. Lonarfanib binds to and inhibits farnesyl transferase, an enzyme involved in the post-translational modification and activation of Ras proteins. Ras proteins participate in numerous signalling pathways (proliferation, cytoskeletal organization), and play an important role in oncogenesis. Mutated ras proteins have been found in a wide range of human cancers.
  • Loncastuximab tesirine - An antibody-drug conjugate (ADC) consisting of an anti-CD19 humanized monoclonal antibody conjugated, via a cleavable linker comprised of valine-alanine and maleimide, to a cytotoxic, cross-linking agent pyrrolobenzodiazepine (PBD) dimer, which targets DNA minor grooves, with potential antineoplastic activity. Upon administration, the monoclonal antibody portion of loncastuximab tesirine targets the cell surface antigen CD19 on various cancer cells. Upon antibody/antigen binding and internalization, the cytotoxic PBD moiety is released. The imine groups of the PBD moiety bind to the N2 positions of guanines on opposite strands of DNA. This induces interstrand cross-links in the minor groove of DNA and inhibits DNA replication, which inhibits the proliferation of CD19-overexpressing tumor cells. CD19, a transmembrane receptor and tumor-associated antigen (TAA), is expressed on a number of B-cell-derived cancers.
  • Long peptide vaccine 7 - A peptide vaccine consisting of a combination of seven synthetic long peptides (SLPs), which are each about 30 amino acids in size, and derived from cancer-testis antigens (CTA) and melanocytic differentiation proteins (MDP), with potential immunostimulating and antitumor activities. Upon administration, long peptide vaccine 7 may stimulate the host immune system to mount a cytotoxic T-cell lymphocyte (CTL) response against tumor cells expressing these peptides. CTA and MDP are overexpressed in a variety of cancer cell types.
  • Long-acting release pasireotide - A long-acting release (LAR) formulation containing pasireotide, a synthetic long-acting cyclohexapeptide, with somatostatin-like activity. Upon intramuscular administration of the LAR formulation of pasireotide, this somatostatin analog strongly binds to and activates somatostatin receptor (SSTR) subtypes 1, 2, 3, and 5. This leads to an inhibition in the secretion of human growth hormone (hGH) and results in decreased production of insulin-like growth factor (IGF-1), which may inhibit IGF-1-mediated cell signaling pathways. This may lead to an inhibition in tumor cell growth and an increase in apoptosis in IGF-1-overexpressing tumor cells. In addition, this agent causes a reduction in adrenocorticotropic hormone (ACTH), which leads to an inhibition of cortisol secretion. ACTH-producing tumors cause hypersecretion of cortisol which results in many unwanted symptoms. This agent may also block other key survival pathways such as the phosphatidylinositol 3-kinase (PI3K) and the mitogen-activated protein kinase (MAPK) signaling pathways. Pasireotide also inhibits vascular endothelial growth factor (VEGF) secretion, thereby decreasing angiogenesis and tumor cell growth in VEGF-overexpressing tumor cells. The long-acting form of pasireotide allows for less frequent administration as compared to the original form of this agent. SSTRs are overexpressed by some neuroendocrine and non-neuroendocrine tumor cells.
  • Lontucirev - An E1B-55kDa-deleted adenovirus that is able to selectively replicate in and lyse TP53-deficient human tumor cells. After tumor cell lysis, released viruses infect neighboring tumor cells, tripping a chain of lontucirev-mediated tumor cell cytotoxicity.
  • Lorlatinib - An orally available, ATP-competitive inhibitor of the receptor tyrosine kinases, anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (Ros1), with potential antineoplastic activity. Upon administration, lorlatinib binds to and inhibits both ALK and ROS1 kinases. The kinase inhibition leads to disruption of ALK- and ROS1-mediated signaling and eventually inhibits tumor cell growth in ALK- and ROS1-overexpressing tumor cells. In addition, PF-06463922 is able to cross the blood brain barrier. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development; ALK dysregulation and gene rearrangements are associated with a series of tumors. ROS1, overexpressed in certain cancer cells, plays a key role in cell growth and survival of cancer cells.
  • Lorukafusp alfa - An immunocytokine comprised of a humanized immunoglobulin G1 (IgG1) chimeric monoclonal antibody directed against the surface disialoganglioside GD2, fused to two human interleukin (IL)-2 molecules with potential antineoplastic and immunomodulatory activities. Upon intravenous administration, the antibody moiety of lorukafusp alfa specifically targets and binds to GD2 expressed on certain tumor cells. This may stimulate the activation of immune effector cells including natural killer (NK) and T-cells, leading to tumor cell death via antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and GD2-specifc T-cell responses. The glycosphingolipid GD2 is a tumor-associated antigen (TAA) overexpressed on the surface of many tumor cells.
  • Lorvotuzumab mertansine - An immunoconjugate of a humanized murine monoclonal antibody (huN-901) and DMI, a semi-synthetic derivative of the plant-derived ansa macrolide maytansine. The antibody moiety of BB-10901 selectively attaches to CD56 antigen, a neural cell adhesion molecule (NCAM)) expressed on the surface of cells of small cell lung cancer (SCLC) and other neuroendocrine (NE) tumors. Thus, the DMI conjugate is targeted specifically to CD56-expressing tumor cells, where it inhibits tubulin polymerization and assembly, resulting in inhibition of mitosis and cell cycle arrest in the S phase.
  • Losatuxizumab vedotin - An antibody-drug conjugate (ADC) composed of an immunoglobulin G1 (IgG1) monoclonal antibody directed against the epidermal growth factor receptor (EGFR), conjugated, via a protease-cleavable peptide linker, to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule inhibitor, with potential antineoplastic activity. Upon administration, the monoclonal antibody moiety of losatuxizumab vedotin selectively targets and binds to EGFR. Upon internalization and proteolytic cleavage, MMAE binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.
  • Losoxantrone - An anthrapyrazole-based antineoplastic antibiotic. Losoxantrone intercalates into DNA, induces single- and double-stranded DNA breaks and inhibits topoisomerase II, thereby inhibiting DNA replication and repair as well as RNA and protein synthesis. Losoxantrone is less cardiotoxic than doxorubicin.
  • Losoxantrone hydrochloride - The hydrochloride salt form of losoxantrone, an anthrapyrazole-based antineoplastic antibiotic. Losoxantrone intercalates into DNA, induces single- and double-stranded DNA breaks and inhibits topoisomerase II, thereby inhibiting DNA replication and repair as well as RNA and protein synthesis. Losoxantrone is less cardiotoxic than doxorubicin.
  • Lovastatin - A lactone metabolite isolated from the fungus Aspergillus terreus with cholesterol-lowering and potential antineoplastic activities. Lovastatin is hydrolyzed to the active beta-hydroxyacid form, which competitively inhibits 3-hydroxyl-3-methylgutarylcoenzyme A (HMG-CoA) reductase, an enzyme involved in cholesterol biosynthesis. In addition, this agent may induce tumor cell apoptosis and inhibit tumor cell invasiveness, possibly by inhibiting protein farnesylation and protein geranylgeranylation, and may arrest cells in the G1 phase of the cell cycle. The latter effect sensitizes tumor cells to the cytotoxic effects of ionizing radiation.
  • Loxl2 inhibitor pat-1251 - An orally available, small-molecule, irreversible inhibitor of lysyl oxidase homolog 2 (lysyl oxidase-like protein 2; LOXL2) with potential antifibrotic activity. Upon oral administration, the aminomethyl pyridine moiety of LOXL2 inhibitor PAT-1251 interacts with the active site of LOXL2 to form a pseudo-irreversible inhibitory complex, thereby inhibiting the catalytic activity of LOXL2. LOXL2, a secreted glycoprotein, catalyzes the post-translational oxidative deamination of lysine residues on target proteins, including collagen and elastin, leading to the formation of deaminated lysine (allysine). Condensation with other allysines or lysines drives the formation of inter- and intramolecular cross-linkages that impact remodeling of the extracellular matrix (ECM), potentially leading to fibrosis. Inhibition of LOXL2, which is often upregulated in fibrotic tissue, may reduce fibrosis in certain chronic fibrotic diseases.
  • Lrp5 antagonist bi 905681 - An antagonist of the lipoprotein receptor-related protein (LRP) 5, with potential antineoplastic and immunomodulating activities. Upon administration, LRP5 antagonist BI 905681 targets and binds to LRP5, thereby blocking the binding of Wnt ligands to LRP5. This prevents the formation of the serpentine receptor Frizzled (FZD)-Wnt-LRP5 trimeric complex and prevents the inactivation of the beta-catenin degradation complex, which leads to beta-catenin degradation. This inhibits the Wnt/beta-catenin signaling pathway, prevents the beta-catenin-mediated activation of Wnt target genes, and inhibits the proliferation and survival of Wnt/beta-catenin-driven tumor cells. In addition, inhibition of Wnt signaling by BI 905681 prevents Wnt-mediated immune escape, thereby re-activating the immune system, specifically inducing the activation of dendritic cells (DCs) and activation as well as infiltration of cytotoxic T-cells into the tumor tissue. The FZD-Wnt-LRP5 trimeric complex induces phosphorylation of LRP5 intracellular domain leading to inactivation of the beta-catenin degradation complex, allowing beta-catenin accumulation; stabilized beta-catenin enters the nucleus and acts as a transcriptional activator of Wnt target genes. Wnt/beta-catenin signaling plays a key role in tumor cell proliferation and survival, and resistance to immunotherapy.
  • Lrp5/6 antagonist bi 905677 - A humanized biparatopic nanobody composed of two blocking domains for the Wnt ligand co-receptors lipoprotein receptor-related proteins (LRP) 5 and 6, with potential antineoplastic and immunomodulating activities. Upon administration, BI 905677 targets and binds to LRP5 and LRP6, thereby blocking the binding of Wnt ligands to LRP5/6. This prevents the activation of the Frizzled (FZD)-Wnt-LRP5/6 trimeric complex and prevents the inactivation of the beta-catenin degradation complex, which leads to beta-catenin degradation. This inhibits the Wnt/beta-catenin signaling pathway, prevents the beta-catenin-mediated activation of Wnt target genes, and inhibits the proliferation and survival of Wnt-driven tumor cells. In addition, inhibition of Wnt signaling by BI 905677 prevents Wnt-mediated immune escape, thereby re-activating the immune system, specifically inducing the activation of dendritic cells (DCs) and activation as well as infiltration of cytotoxic T-cells into the tumor tissue. The FZD-Wnt-LRP5/6 trimeric complex induces phosphorylation of LRP5 or LRP6 intracellular domains leading to inactivation of the beta-catenin degradation complex, allowing beta-catenin accumulation; stabilized beta-catenin enters the nucleus and acts as a transcriptional activator of Wnt target genes. Wnt/beta-catenin signaling plays a key role in tumorigenesis and resistance to immunotherapy.
  • Lsd1 inhibitor cc-90011 - An orally available inhibitor of lysine specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, CC-90011 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the di- and mono-methylated forms of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4, respectively. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor (remove hyphen) suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. In addition, LSD1 demethylates mono- or di-methylated H3K9 which increases gene expression of tumor promoting genes; inhibition of LSD1 promotes H3K9 methylation and decreases transcription of these genes. LSD1, an enzyme belonging to the flavin adenine dinucleotide (FAD)-dependent amine oxidase family that is overexpressed in certain tumor cells, plays a key role in tumor cell growth and survival.
  • Lsd1 inhibitor gsk2879552 - An orally available, irreversible, inhibitor of lysine specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, GSK2879552 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the dimethylated form of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor-suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. LSD1, overexpressed in certain tumor cells, plays a key role in tumor cell growth and survival.
  • Lsd1 inhibitor syha1807 - An orally available inhibitor of lysine-specific demethylase 1 (LSD1; KDM1A), with potential antineoplastic activity. Upon oral administration, LSD1 inhibitor SYHA1807 targets, binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the di- and mono-methylated forms of lysine at position 4 of histone 3 (H3K4) to mono- and unmethylated H3K4, respectively. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. In addition, LSD1 demethylates mono- or di-methylated H3K9 which increases gene expression of tumor promoting genes; inhibition of LSD1 promotes H3K9 methylation and decreases transcription of these genes. LSD1 is overexpressed in a number of tumor cell types. LSD1 acts on histone H3 as a transcription co-repressor through demethylation of lysine 4 (H3K4) or as a transcription co-activator through demethylation of lysine 9 (H3K9).
  • Lucanthone - An orally available thioxanthone-based DNA intercalator and inhibitor of the DNA repair enzyme apurinic-apyrimidinic endonuclease 1 (APEX1 or APE1), with anti-schistosomal and potential antineoplastic activity. Lucanthone intercalates DNA and interferes with the activity of topoisomerases I and II during replication and transcription, thereby inhibiting the synthesis of macromolecules. In addition, this agent specifically inhibits the endonuclease activity of APE1, without affecting its redox activity, resulting in un-repaired DNA strand breaks which may induce apoptosis. Therefore, lucanthone may sensitize tumor cells to radiation and chemotherapy. Furthermore, lucanthone inhibits autophagy through the disruption of lysosomal function. The multifunctional nuclease APE1 is a key component for DNA repair; its expression is often correlated with tumor cell resistance to radio- and chemotherapy.
  • Lucatumumab - A fully human monoclonal antibody directed against the B-cell surface antigen CD40 with potential antineoplastic activity. Lucatumumab binds to and inhibits CD40, thereby inhibiting CD40 ligand-induced cell proliferation and triggering cell lysis via antibody-dependent cellular cytotoxicity (ADCC) in cells overexpressing CD40. CD40, an integral membrane protein found on the surface of B lymphocytes, is a member of the tumor necrosis factor receptor superfamily and is highly expressed in a number of B-cell malignancies.
  • Lucitanib - A novel dual inhibitor targeting human vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs) with antiangiogenic activity. Lucitanib inhibits VEGFR-1, -2, -3 and FGFR-1, -2 kinases in the nM range, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation, and the induction of tumor cell death. Both VEGFRs and FGFRs belong to the family of receptor tyrosine kinases that may be upregulated in various tumor cell types.
  • Luminespib - A derivative of 4,5-diarylisoxazole and a third-generation heat shock protein 90 (Hsp90) inhibitor with potential antineoplastic activity. Luminespib has been shown to bind with high affinity to and inhibit Hsp90, resulting in the proteasomal degradation of oncogenic client proteins; the inhibition of cell proliferation; and the elevation of heat shock protein 72 (Hsp72) in a wide range of human tumor cell lines. Hsp90, a 90 kDa molecular chaperone, plays a key role in the conformational maturation, stability and function of other substrate or "client" proteins within the cell, many of which are involved in signal transduction, cell cycle regulation and apoptosis, including kinases, transcription factors and hormone receptors. Hsp72 exhibits anti-apoptotic functions; its up-regulation may be used as a surrogate marker for Hsp90 inhibition.
  • Luminespib mesylate - The mesylate salt of luminespib, a derivative of 4,5-diarylisoxazole and a third-generation heat shock protein 90 (Hsp90) inhibitor with potential antineoplastic activity. Upon administration, luminespib binds with high affinity to and inhibits Hsp90, resulting in the proteasomal degradation of oncogenic client proteins; the inhibition of cell proliferation; and the elevation of heat shock protein 72 (Hsp72) in a wide range of human tumor cell lines. Hsp90, a 90 kDa molecular chaperone, plays a key role in the conformational maturation, stability and function of other substrate or "client" proteins within the cell, many of which are involved in signal transduction, cell cycle regulation and apoptosis, including kinases, transcription factors and hormone receptors. Hsp72 exhibits anti-apoptotic functions; its up-regulation may be used as a surrogate marker for Hsp90 inhibition.
  • Lumretuzumab - An immunoconjugate containing a glycoengineered, humanized monoclonal antibody directed against the human epidermal growth factor receptor HER3 (ErbB3), with potential antineoplastic activity. Upon administration, lumretuzumab binds to the extracellular domain of HER3 and inhibits HER3 dimerization; thereby, preventing EGFR-dependent signaling. In addition, RO5479599 stimulates the immune system to exert antibody-dependent cellular cytotoxicity (ADCC). This may decrease proliferation of HER3-overexpressing tumor cells. HER3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in tumors; it has no active kinase domain but is activated through heterodimerization with other members of the EGFR receptor family, such as HER2.
  • Lung tumor associated antigen - A tumor associated antigen derived from the cell surface antigen of lung cancer cells. Lung tumor associated antigen could be used as a diagnostic marker or as a form of immunotherapy targeted against lung cancer cells.
  • Lung-targeted immunomodulator qbkpn - A proprietary, lung-targeted, site specific immunomodulator (SSI), with potential immunostimulating and antineoplastic activities. Although the exact type and composition of the lung-targeted immunomodulator QBKPN has yet to be fully disclosed, upon subcutaneous administration, this agent is able to activate a local innate immune response in the lung tissue. This results in an increased number of M1 macrophages, which induces a shift from M2 to M1 macrophage dominance in the tumor microenvironment, and stimulates the recruitment of other immune cells. The M1 macrophages exert antitumor activity and eradicate lung cancer cells through phagocytosis. QBKPN does not induce a systemic immune response or affect other organs or tissues. Altogether, this SSI may decrease tumor cell growth in the lungs. SSIs contain specific, inactivated components of pathogens, such as bacteria and/or viruses, which normally cause an acute infection in the specific organ or tissue of interest.
  • Lupartumab amadotin - An antibody-drug conjugate (ADC) composed of an antibody against a structural homolog of the urokinase-type plasminogen activator receptor (uPAR) and tumor-associated antigen, C4.4a, and conjugated with a cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, lupartumab amadotin targets and binds to C4.4a-expressing tumor cells. Upon binding and cell entry, the cytotoxic agent kills the tumor cell. C4.4a, a glycolipid-anchored membrane protein and a member of the Ly-6 family, is overexpressed by a variety of cancer cell types whereas it is minimally expressed on healthy cells.
  • Lurbinectedin - A synthetic tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-one alkaloid analogue with potential antineoplastic activity. Lurbinectedin covalently binds to residues lying in the minor groove of DNA, which may result in delayed progression through S phase, cell cycle arrest in the G2/M phase and cell death.
  • Lurtotecan - A semisynthetic analogue of camptothecin with antineoplastic activity. Lurtotecan selectively stabilizes the topoisomerase I-DNA covalent complex and forms an enzyme-drug-DNA ternary complex. As a consequence of the formation of this complex, both the initial cleavage reaction and religation steps are inhibited and subsequent collision of the replication fork with the cleaved strand of DNA results in inhibition of DNA replication, double strand DNA breakage and triggering of apoptosis. Independent from DNA replication inhibition, lurtotecan also inhibits RNA synthesis, multi-ubiquitination and degradation of topoisomerase I and chromatin reorganization.
  • Lurtotecan liposome - A liposome-encapsulated formulation of lurtotecan with antineoplastic activity. Lurtotecan, a semisynthetic analogue of camptothecin, selectively stabilizes the topoisomerase I-DNA covalent complex and forms an enzyme-drug-DNA ternary complex during S phase of the cell cycle, thereby inhibiting religation of topoisomerase I-mediated single-stranded DNA breaks. This ultimately results in an inhibition of DNA replication, inducing double-stranded DNA breakages, obstruction of RNA and protein synthesis and triggering apoptosis. Furthermore, this agent also stimulates degradation of topoisomerase I, likely mediated through ubiquitin-proteasomal pathway. Liposomal delivery of lurtotecan improves its penetration and delivery into tumors while lowering systemic side effects.
  • Lutetium lu 177 anti-ca19-9 monoclonal antibody 5b1 - A radioimmunoconjugate comprised of a human monoclonal antibody (huMAb-5B1) against the carbohydrate antigen sialyl Lewis A (carbohydrate antigen 19-9; CA19-9) that is conjugated to the chelator 2-(p-isothiocyanatobenzyl)-cyclohexyl-diethylenetriaminepentaacetic acid (CHX-A-DTPA) and labeled with the beta-emitting radioisotope lutetium Lu 177 (Lu 177), with radioisotopic activity and potential use as an antineoplastic radiotherapeutic and an imaging agent in both planar imaging and single-photon emission computed tomography (SPECT). The antibody moiety of Lu 177 anti-CA19-9 monoclonal antibody 5B1 targets and binds to CA19-9-expressing tumor cells. This may promote killing of CA19-9-expressing tumor cells through the local induction of both complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Additionally, upon binding and internalization, the Lu 177 moiety can deliver a cytotoxic dose of beta radiation to the CA19-9-expressing tumor cells. Furthermore, the radioisotope moiety may be imaged using planar imaging and SPECT, thus allowing evaluation of the pharmacokinetic profile of the agent, and the imaging and quantification of CA19-9-expressing tumor cells, respectively. CA19-9, a Lewis-type carbohydrate antigen overexpressed on a number of different tumor cell types, plays a key role in tumor cell survival and metastasis.
  • Lutetium lu 177 dota-biotin - A radioconjugate of biotin conjugated with the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA) and labeled with the beta-emitting isotope lutetium Lu 177 (Lu-177) that can be used for radioimmunotherapeutic purposes. Lutetium Lu 177 DOTA-biotin could be used in pre-targeting radioimmunotherapy, which pretreats the lesion with oxidized avidin that binds to protein amino groups on cells. As avidin binds to biotin, the radioisotope can be selectively delivered to cancer cells leading to tumor cell eradication.
  • Lutetium lu 177 dota-ipn01087 - A radioconjugate consisting of the neurotensin receptor type 1 (NTR1) antagonist, IPN01087 (3BP-227), that is linked, via the chelating agent, dodecanetetraacetic acid (DOTA), to the beta-emitting radioisotope lutetium Lu 177, with potential antineoplastic activity and imaging activity during positron emission tomography/computed tomography (PET/CT). Upon administration, lutetium Lu 177-DOTA-IPN01087 binds to NTR1 expressed on certain tumor cells. Upon binding and internalization, this radioconjugate specifically delivers a cytotoxic dose of beta radiation to NTR1-expressing cells. NTR1, a G-protein coupled receptor, is highly expressed in ductal pancreatic adenocarcinoma but not in normal pancreatic tissue.
  • Lutetium lu 177 dota-n3-ctt1403 - A radioconjucate consisting of CTT1403, a phosphoramidate-based irreversible inhibitor of human prostate-specific membrane antigen with an albumin binding moiety, connected via click chemistry to lutetium Lu 177-dodecanetetraacetic acid-azide (177Lu-DOTA-N3), with potential antineoplastic activity. Upon administration, lutetium Lu 177-DOTA-N3-CTT1403 targets and binds to PSMA expressed on tumor cells via its CTT1403 moiety, and upon internalization, delivers cytotoxic beta radiation directly to PSMA-expressing tumor cells. PSMA, a tumor-associated antigen (TAA) and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on most prostate tumor cells. The albumin binding motif extends circulation half-life thereby improving tumor cell uptake of the radioconjugate.
  • Lutetium lu 177 dotatate - A radioconjugate consisting of the tyrosine-containing somatostatin analog Tyr3-octreotate (TATE) conjugated with the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA) and radiolabeled with the beta-emitting radioisotope lutetium Lu 177, with potential imaging and antineoplastic activities. Lutetium Lu 177 dotatate binds to somatostatin receptors (SSTRs), with high affinity to type 2 SSTR, present on the cell membranes of many types of neuroendocrine tumor (NET) cells. Upon binding and internalization, this radioconjugate specifically delivers a cytotoxic dose of beta radiation to SSTR-positive cells. Tyr3-octreotate (TATE) is an octreotide derivative in which phenylalanine at position 3 is substituted by tyrosine and position 8 threoninol is replaced with threonine. SSTRs have been shown to be present in large numbers on NET and their metastases, while most other normal tissues express low levels of SSTRs.
  • Lutetium lu 177 dota-tetulomab - A radioimmunoconjugate, which consists of a monoclonal antibody against the cell-surface antigen CD37 covalently linked, via the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA), to the beta-emitting radioisotope lutetium Lu 177, with potential antineoplastic activity. The antibody moiety of lutetium Lu 177 DOTA-tetulomab binds to CD37 on tumor B-cells. Upon internalization, the radioisotope moiety delivers a cytotoxic dose of beta radiation to CD37-expressing tumor cells. CD37, a transmembrane glycoprotein, is overexpressed in B-cell malignancies.
  • Lutetium lu 177 lilotomab-satetraxetan - A radioconjugate consisting of lilotomab, a murine immunoglobulin G1 (IgG1) antibody directed against the CD37 antigen, conjugated via the chelating agent 2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (p-SCN-Bn-DOTA) with potential antineoplastic activities. Upon administration of lutetium Lu 177 lilotomab-satetraxetan, the lilotomab moiety binds to CD37 expressed on certain tumor cells. Upon binding, lutetium Lu 177 lilotomab-satetraxetan delivers a cytotoxic dose of beta radiation to CD37-expressing cells. CD37 is a transmembrane glycoprotein expressed at high-levels on B-cells and to a lesser extent on T-cells and myeloid cells, and is frequently overexpressed in certain B-cell lymphomas.
  • Lutetium lu 177 monoclonal antibody cc49 - A radioimmunoconjugate of the humanized monoclonal antibody (MoAb) CC49 labeled with lutetium 131 (Lu-177). MoAb CC49 binds to the pancarcinoma tumor-associated glycoprotein (TAG)-72 with high affinity. Lu-177 MoAb CC49 delivers gamma radiation emitting Lu-177 nuclide directly to tumor cells that express TAG-72, and so may be used in radioimmunotherapeutic treatment of cancers.
  • Lutetium lu 177 monoclonal antibody j591 - A radioimmunoconjugate consisting of a humanized monoclonal antibody directed against the extracellular domain of prostate-specific membrane antigen linked to a beta-emitting radioisotope (lutetium-177). This radioimmunoconjugate binds to tumor cells that express the extracellular domain of prostate-specific membrane antigen, delivering beta particle radiation selectively to tumor cells expressing this antigen and so limiting the exposure of normal tissues to ionizing radiation.
  • Lutetium lu 177 pp-f11n - A radioconjugate composed of PP-F11N, a gastrin analog, conjugated to the beta-emitting radioisotope lutetium Lu 177, with potential antineoplastic activity and potential use as an imaging agent for scintigraphy. Following intravenous administration, the PP-F11N moiety binds to the cholecystokinin-2 (CCK-2) receptor. Subsequently, the CCK-2 receptor-expressing tumor cells can be visualized scintigraphically. In addition, the radioisotope moiety delivers a cytotoxic dose of beta radiation to CCK-2 receptor-expressing tumor cells. CCK-2 receptors are expressed on a variety of tumor cell types.
  • Lutetium lu 177 satoreotide tetraxetan - A radioconjugate consisting of the somatostatin antagonistic peptide satoreotide tetraxetan (JR11) that is linked, via the chelating agent dodecanetetraacetic acid (DOTA), to the beta-emitting radioisotope lutetium Lu 177, with potential antineoplastic activity and imaging activity during positron emission tomography/computed tomography (PET/CT). Upon administration, lutetium Lu 177-DOTA-JR11 binds to somatostatin receptors (SSTRs), with high affinity for SSTR2, present on the cell membranes of many types of neuroendocrine tumor (NET) cells. Upon binding and internalization, this radioconjugate specifically delivers a cytotoxic dose of beta radiation to SSTR-positive cells. SSTRs have been shown to be present in large numbers on NETs and their metastases, while most normal tissues express low levels of SSTRs.
  • Lutetium lu 177-dota-eb-tate - A radioconjugate consisting of Evans blue (EB) modified, tyrosine-containing somatostatin analog, Tyr3-octreotate (TATE), conjugated with the bifunctional, macrocyclic chelating agent tetra-azacyclododecane tetraacetic acid (DOTA), and radiolabeled with the beta-emitting radioisotope lutetium Lu 177, with potential imaging and antineoplastic activities. Upon intravenous administration, Lutetium Lu 177-DOTA-EB-TATE binds to somatostatin receptors (SSTRs), with high affinity to type 2 SSTRs (SSTR2s), present on the cell membranes of many neuroendocrine tumor (NET) cells. Upon binding and internalization, this radioconjugate specifically delivers a cytotoxic dose of beta radiation to SSTR2-positive cells. The incorporation of an albumin-binding moiety through EB modification allows Lutetium Lu 177-DOTA-EB-TATE to reversibly bind to endogenous albumin, potentially extending half-life and increasing targeted accumulation of the drug in tumors. SSTRs, especially SSTR2s, are expressed at relatively higher levels in many tumor cell types and tumor blood vessels, compared to normal tissues.
  • Lutetium lu 177-dtpa-omburtamab - A radioimmunoconjugate consisting of omburtamab, a murine immunoglobulin G1 (IgG1) antibody directed against the surface immunomodulatory glycoprotein human B7-homolog 3 (B7-H3, CD276), conjugated, via the chelating agent diethylenetriaminepentaacetic acid (DTPA), to the radioisotope lutetium Lu 177, with potential antineoplastic activity. Upon intracerebroventricular administration of lutetium Lu 177-DTPA-omburtamab, the omburtamab moiety binds to B7-H3 expressed on certain tumor cells. Upon binding, lutetium Lu 177-DTPA-omburtamab delivers a cytotoxic dose of beta radiation to B7-H3-expressing cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells but is minimally expressed by normal human tissues. B7-H3 is a negative regulator of T-cell activation; its overexpression plays a key role in immuno-evasion, tumor cell invasion and metastasis, and is correlated with poor prognosis.
  • Lutetium lu 177-edotreotide - A radioconjugate consisting of the somatostatin analogue edotreotide labeled with lutetium Lu 177 with potential antineoplastic activities. Lutetium Lu 177-edotreotide binds to somatostatin receptors (SSTRs), with high affinity to type 2 SSTR, present on the cell membranes of many types of neuroendocrine tumor cells. Upon binding and internalization, this radioconjugate specifically delivers a cytotoxic dose of beta radiation to SSTR-positive cells. Edotreotide is produced by substituting tyrosine for phenylalanine at the 3 position of the somatostatin analogue octreotide (Tyr3-octreotide or TOC) and chelated by the bifunctional, macrocyclic chelating agent dodecanetetraacetic acid (DOTA).
  • Lutetium lu 177-neob - A radioconjugate consisting of the gastrin-releasing peptide receptor (GRPR) antagonist, NeoB, linked via the chelating agent, dodecanetetraacetic acid (DOTA), to the beta-emitting radioisotope lutetium Lu 177, with potential antineoplastic activity. Upon administration, lutetium Lu 177 NeoB targets and binds to GRPRs present on certain tumor cells. Upon binding and internalization, this radioconjugate specifically delivers a cytotoxic dose of beta radiation to GRPR-expressing cells. GRPR, also known as bombesin receptor subtype 2, is a G protein-coupled receptor that is overexpressed in some cancer types.
  • Lutetium lu 177-psma-617 - A radioconjugate composed of PSMA-617, a human prostate-specific membrane antigen (PSMA)-targeting ligand, conjugated to the beta-emitting radioisotope lutetium Lu 177 (177Lu), with potential antineoplastic activity against PSMA-expressing tumor cells. Upon intravenous administration of 177Lu-PSMA-617, the PSMA-617 moiety targets and binds to PSMA-expressing tumor cells. Upon binding, PSMA-expressing tumor cells are destroyed by 177Lu through the specific delivery of beta particle radiation. PSMA, a tumor-associated antigen and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells.
  • Lutetium lu-177 capromab - A radioimmunoconjugate consisting of capromab linked to lutetium Lu 177 via the bifunctional macrocyclic chelator methoxy-tetraazacyclododecane-tetraacetic acid (MeO-DOTA) with potential antineoplastic activity. Lutetium Lu 177-capromab binds to human prostate specific membrane antigen (PSMA) expressed on tumor cell surfaces via its capromab moiety and, upon internalization, delivers cytotoxic beta radiation directly to PSMA-expressing tumor cells. PSMA is a cell surface glycoprotein abundantly expressed by prostate epithelium and is typically overexpressed by prostate cancer cells.
  • Lutetium lu-177 girentuximab - A radioimmunoconjugate consisting of the chimeric monoclonal antibody cG250 linked to the low energy beta-emitting radioisotope Lutetium 177, via the bifunctional macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA), with potential antineoplastic activity. The antibody moiety of lutetium Lu-177-DOTA-chimeric monoclonal antibody cG250 binds to renal cell carcinoma (RCC) cells expressing the RCC-associated antigen G250; a cytotoxic dose of beta radiation is selectively delivered to G250-expressing RCC cells upon internalization of the radioimmunoconjugate.
  • Lutetium lu-177 psma-r2 - A radioconjugate composed of PSMA-R2, a human prostate-specific membrane antigen (PSMA)-targeting ligand, conjugated to the beta-emitting radioisotope lutetium Lu 177 (177Lu), with potential antineoplastic activity against PSMA-expressing tumor cells. Upon intravenous administration of 177Lu-PSMA-R2, the PSMA-R2 moiety targets and binds to PSMA-expressing tumor cells. Upon binding, PSMA-expressing tumor cells are destroyed by 177Lu through the specific delivery of beta particle radiation. PSMA, a tumor-associated antigen (TAA) and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on the majority of prostate tumor cells.
  • Lutetium lu-177 rituximab - A radioconjugate composed of rituximab, a recombinant chimeric murine/human immunoglobulin G1 (IgG1) antibody directed against the CD20 antigen, conjugated to the beta-emitting radioisotope lutetium Lu 177, with potential antineoplastic activity. Upon administration, the rituximab moiety targets and binds to CD20 expressed on tumor cells and delivers a cytotoxic dose of beta radiation to CD20-expressing cells. CD20 is expressed on the surface of pre-B and mature B-lymphocytes and is overexpressed in a variety of B-cell malignancies.
  • Lv.il-2/b7.1-transduced aml blast vaccine rfusin2-aml1 - A whole-cell cancer vaccine, containing human acute myeloid leukemic (AML) blasts that have been genetically engineered to express a B7.1/IIL-2 fusion protein encoded by a self-inactivating lentiviral vector (LV), with potential antineoplastic and immunomodulating activities. Upon administration, LV.IL-2/B7.1-transduced AML blast vaccine RFUSIN2-AML1 may stimulate a host cytotoxic T lymphocyte (CTL) response against AML cells. The single fusion protein encoded by the LV is postsynthetically cleaved to produce biologically active membrane-anchored B7.1 and secreted IL-2 in AML blasts; combined expression of IL-2 and the co-stimulatory molecule B7.1 by AML blasts may increase stimulation of both allogeneic and autologous cytotoxic T cells.
  • Ly6k/vegfr1/vegfr2 multipeptide vaccine - A multipeptide vaccine consisting of peptides derived from lymphocyte antigen 6 complex locus K (LY6K) and type I and II vascular endothelial growth factor receptors (VEGFRs) with potential antineoplastic activity. Upon administration, LY6K/VEGFR1/VEGFR2 multipeptide vaccine may elicit an antitumor cytotoxic T-lymphocyte (CTL) immune response against LY6K-expressing tumor cells and/or VEGFR-expressing vascular endothelial cells involved in tumor angiogenesis. LY6K is a tumor-associated antigen (TAA) that occurs singly in glycosylphosphatidyl-inositol (GPI)-linked cell-surface glycoproteins or as three-fold repeated domain in the urokinase-type plasminogen activator receptor; VEGFRs are cell surface receptors that stimulate endothelial cell proliferation, invasion, angiogenesis, and vasculogenesis upon ligand binding and receptor activation.
  • Lymphodepleted autologous cd4-directed car t cells - A preparation of autologous peripheral blood T-lymphocytes (PBTLs) that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the T-cell surface antigen CD4, administered with lymphodepletion, with potential immunostimulating and antineoplastic activities. Upon administration, lymphodepleted autologous CD4-directed CAR T cells specifically recognize and kill CD4-expressing tumor cells. CD4, a tumor-associated antigen (TAA), is overexpressed in various lymphomas, including peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and anaplastic large cell lymphoma.
  • Lymphoma taa-specific cytotoxic t lymphocytes - A population of autologous cytotoxic T lymphocytes (CTLs) with potential immunomodulating and antitumor activities. White blood cells are grown ex-vivo and are exposed to dendritic cells (DCs) loaded with lymphoma tumor associated antigens (TAAs); the TAA-specific CTLs are further expanded ex-vivo before being introduced into the patient. Upon infusion with TAA-specific CTLs, these CTLs may help activate tumor-specific CTL responses in the patient, thereby specifically killing TAA-expressing cancer cells and eventually inhibiting tumor cell proliferation.
  • Lyophilized black raspberry lozenge - A lozenge containing lyophilized black raspberry with potential antioxidant, pro-apoptotic, anti-angiogenic and chemopreventive activities. In addition to vitamins, minerals and phytosterols, black raspberries are rich in phenolic acids, such as gallic acid, ellagic acid, proanthocyanidins, and flavonoids. The anthocyanins appear to contribute significantly to this agent's effects. Anthocyanins inhibit both the activation of several signal transduction pathways, including the mitogen-activated protein kinase-mediated pathways, and certain transcription factors, such as nuclear factor kappa B (NF-kB), activator protein-1 (AP-1) complex, and nuclear factor in activated T-cells (NFAT). This inhibitory activity modulates the expression of downstream target genes that are upregulated in a variety of cancer cell types, including inducible nitric oxide synthase, cyclooxygenase-2, vascular endothelial growth factor and the anti-apoptotic protein survivin.
  • Lyophilized black raspberry saliva substitute - A saliva substitute (or artificial saliva) containing lyophilized black raspberry with potential antioxidant, pro-apoptotic and chemopreventive activities. In addition to vitamins, minerals and phytosterols, black raspberries are rich in flavonols of which the anthocyanins appear to contribute significantly to this agent's chemopreventive effects. Anthocyanins inhibit the activation of several signal transduction pathways, including the mitogen-activated protein kinase-mediated pathways, and certain transcription factors, such as nuclear factor kappa B (NF-kB), activator protein-1 (AP-1) complex, and nuclear factor in activated T-cells (NFAT). This in turn modulates the expression of downstream target genes that are upregulated in a variety of cancer cell types, including inducible nitric oxide synthase, cyclooxygenase-2, vascular endothelial growth factor and the anti-apoptotic protein survivin.
  • Lysine-specific demethylase 1 inhibitor incb059872 - An orally available inhibitor of lysine-specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, INCB059872 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the di- and mono-methylated forms of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4, respectively, through amine oxidation. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor-suppressor genes. In addition, LSD1 demethylates mono- or di-methylated H3K9 which increases gene expression of tumor promoting genes; inhibition of LSD1 promotes H3K9 methylation and decreases transcription of these genes. Altogether, this may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. LSD1, an enzyme belonging to the flavin adenine dinucleotide (FAD)-dependent amine oxidase family, is overexpressed in certain tumor cells and plays a key role in the regulation of gene expression and in tumor cell growth and survival.
  • Lyso-thermosensitive liposome doxorubicin - A temperature-sensitive liposomal formulation of the anthracycline antibiotic doxorubicin with potential antineoplastic activity. Upon intravenous administration, circulating thermosensitive liposomes are activated locally by increasing the tumor temperature to 40-41 degrees Celsius using an external heat source. The elevated temperature causes compositional changes in the liposomes, creating openings that allow for the release of encapsulated doxorubicin. Compared to non-thermosensitive liposomes, lyso-thermosensitive liposomes deliver higher concentrations of a cytotoxic agent to a heat-treated tumor site while sparing normal tissues unexposed to heat treatment.

Alphabetic list of antineoplastic agents - 0-9 - A1 - A2 - A3 - A4 - A5 -A6 - B - C - D - E - F - G - H - I - JK - L - M - NO - PQ - R - S - T - UVW - XYZ

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