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Antineoplastic agents a1

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  • A2a receptor antagonist eos100850 - An orally bioavailable immune checkpoint inhibitor and antagonist of the adenosine A2A receptor (A2AR; ADORA2A), with potential immunomodulating and antineoplastic activities. Upon administration, A2AR antagonist EOS100850 selectively binds to and inhibits A2AR expressed on T-lymphocytes. This prevents tumor-released adenosine from interacting with the A2A receptors, thereby blocking the adenosine/A2AR-mediated inhibition of T-lymphocytes. This results in the proliferation and activation of T-lymphocytes, and stimulates a T-cell-mediated immune response against tumor cells. A2AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of T-cells and, upon activation by adenosine, inhibits their proliferation and activation. Adenosine is often overproduced by cancer cells and plays a key role in immunosuppression.
  • A-65 - An amide analogue of Trichostatin A studied for potential antineoplastic activity. A-65 inhibits zinc-dependent histone deacetylase, inducing terminal cell differentiation and anti-angiogenic activity.
  • Abagovomab - A murine IgG1 monoclonal anti-idiotype antibody, containing a variable antigen-binding region that functionally mimics the three-dimensional structure of a specific epitope on the ovarian cancer tumor-associated antigen CA-125, with potential antineoplastic activity. With a variable antigen-binding region that acts as a surrogate antigen for CA-125, abagovomab may stimulate the host immune system to elicit humoral and cellular immune responses against CA-125-positive tumor cells, resulting in inhibition of tumor cell proliferation.
  • Abarelix - A synthetic decapeptide and antagonist of naturally occurring gonadotropin-releasing hormone (GnRH). Abarelix directly and competitively binds to and blocks the gonadotropin releasing hormone receptor in the anterior pituitary gland, thereby inhibiting the secretion and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). In males, the inhibition of LH secretion prevents the release of testosterone. As a result, this may relieve symptoms associated with prostate hypertrophy or prostate cancer, since testosterone is required to sustain prostate growth.
  • Abemaciclib - An orally available cyclin-dependent kinase (CDK) inhibitor that targets the CDK4 (cyclin D1) and CDK6 (cyclin D3) cell cycle pathway, with potential antineoplastic activity. Abemaciclib specifically inhibits CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation in early G1. Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth. Overexpression of the serine/threonine kinases CDK4/6, as seen in certain types of cancer, causes cell cycle deregulation.
  • Abemaciclib mesylate - The mesylate salt of abemaciclib, an orally available cyclin-dependent kinase (CDK) inhibitor that targets the cyclin D1-CDK4 and cyclin D3-CDK6 cell cycle pathway, with potential antineoplastic activity. Abemaciclib specifically inhibits CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation in early G1. Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth. Overexpression of the serine/threonine kinases CDK4/6, as seen in certain types of cancer, causes cell cycle deregulation.
  • Abexinostat - An orally bioavailable hydroxamate-based pan-inhibitor of histone deacetylase (HDAC), with potential antineoplastic and radiosensitizing activities. Upon administration, abexinostat inhibits HDAC, resulting in an accumulation of highly acetylated histones, followed by the induction of chromatin remodeling; the selective transcription of tumor suppressor genes; and the tumor suppressor protein-mediated inhibition of tumor cell division and induction of tumor cell apoptosis. In addition, abexinostat decreases the expression of the DNA-repair protein RAD51, thereby reducing the RAD51 protein, preventing repair of DNA double-strand breaks and increasing sensitivity of tumor cells to DNA damaging agents. HDAC, upregulated in many tumor types, is an enzyme that is responsible for the deacetylation of chromatin histone proteins.
  • Abexinostat tosylate - The tosylate salt form of abexinostat, an orally bioavailable hydroxamate-based pan-inhibitor of histone deacetylase (HDAC), with potential antineoplastic and radiosensitizing activities. Upon administration, abexinostat inhibits HDAC, resulting in an accumulation of highly acetylated histones, followed by the induction of chromatin remodeling; the selective transcription of tumor suppressor genes; and the tumor suppressor protein-mediated inhibition of tumor cell division and induction of tumor cell apoptosis. In addition, abexinostat decreases the expression of the DNA-repair protein RAD51, thereby reducing the RAD51 protein, preventing repair of DNA double-strand breaks and increasing sensitivity of tumor cells to DNA damaging agents. HDAC, upregulated in many tumor types, is an enzyme that is responsible for the deacetylation of chromatin histone proteins.
  • Abiraterone - A steroidal compound with antiandrogen activity. Abiraterone inhibits the enzymatic activity of steroid 17alpha-monooxygenase (17alpha-hydrolase/C17,20 lyase complex; CYP17A1), a member of the cytochrome p450 family that catalyzes the 17alpha-hydroxylation of steroid intermediates involved in testosterone synthesis. Administration of this agent may suppress testosterone production by both the testes and the adrenals to castrate-range levels.
  • Abiraterone acetate - An orally active acetate ester form of the steroidal compound abiraterone with antiandrogen activity. Abiraterone inhibits the enzymatic activity of steroid 17alpha-monooxygenase (17alpha-hydrolase/C17,20 lyase complex), a member of the cytochrome p450 family that catalyzes the 17alpha-hydroxylation of steroid intermediates involved in testosterone synthesis. Administration of this agent may suppress testosterone production by both the testes and the adrenals to castrate-range levels.
  • Abituzumab - A humanized monoclonal antibody directed against the human alpha v integrin subunit with potential antiangiogenic and antineoplastic activities. Abituzumab, a chimeric antibody which includes the antigen binding sites of the anti-integrin mouse antibody 17E6, binds to and inhibits the activity of alphaVbeta3 integrin (vitronectin receptor); this may result in the inhibition of endothelial cell-cell interactions, endothelial cell-matrix interactions, and integrin-mediated tumor angiogenesis and metastasis in alphavbeta3-expressing tumor cells. AlphaVbeta3 integrin, a cell adhesion and signaling receptor, is expressed on the surface of tumor vessel endothelial cells and plays a crucial role in endothelial cell adhesion and migration.
  • Acai berry juice - A juice product obtained from the fruit of the acai palm tree (Euterpe oleracea) with anti-inflammatory, antioxidant and potential chemopreventive activities. Besides high amounts of vitamins, minerals and fatty acids, acai berry is rich in phytonutrients such as anthocyanins and flavones which are potent scavengers of reactive oxygen species. The fruit also contains high amounts of the flavone velutin which exhibits potent anti-inflammatory properties. Velutin is able to inhibit the degradation of the inhibitor of nuclear factor kappa-B (NF-kB), thereby blocking the activation of NF-kB, as well as inhibiting phosphorylation of mitogen-activated protein kinase p38 and JNK. Inhibition of these processes results in suppression of the production of proinflammatory cytokines, such as tumor necrosis factor alpha and interleukin 6.
  • Acalabrutinib - An orally available inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, acalabrutinib inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.
  • Acalisib - An inhibitor of the beta and delta isoforms of the 110 kDa catalytic subunit of class IA phosphoinositide-3 kinases (PI3K) with potential immunomodulating and antineoplastic activities. Acalisib inhibits the activity of PI3K, thereby preventing the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3), which decreases tumor cell proliferation and induces cell death. PI3K-mediated signaling is often dysregulated in cancer cells; the targeted inhibition of PI3K is designed to preserve PI3K signaling in normal, non-neoplastic cells.
  • Aceglatone - A derivative of D-glucaro-1, 4-lactone with chemopreventive and anti-tumor activities. One of the key processes in which human body eliminates toxic chemicals as well as hormones (such as estrogen) is by glucuronidation. When beta-glucuronidase deconjugates these glucuronides, it prolongs the stay of the hormone or toxic chemical in the body. Elevated beta-glucuronidase activity has been implicated to be associated with an increased risk for hormone-dependent cancers like breast, prostate, and colon cancers. Thereby, aceglatone may suppress the developments of hormone-dependent cancers mediated through beta-glucuronidase inhibition.
  • Acetylcysteine - A synthetic N-acetyl derivative of the endogenous amino acid L-cysteine, a precursor of the antioxidant enzyme glutathione. Acetylcysteine regenerates liver stores of glutathione. This agent also reduces disulfide bonds in mucoproteins, resulting in liquification of mucus. Some evidence suggests that acetylcysteine may exert an anti-apoptotic effect due to its antioxidant activity, possibly preventing cancer cell development or growth. In addition, acetylcysteine has inhibited viral stimulation by reactive oxygen intermediates, thereby producing antiviral activity in HIV patients.
  • Acitretin - An orally-active metabolite of the synthetic aromatic retinoic acid agent etretinate with potential antineoplastic, chemopreventive, anti-psoratic, and embryotoxic properties. Acitretin activates nuclear retinoic acid receptors (RAR), resulting in induction of cell differentiation, inhibition of cell proliferation, and inhibition of tissue infiltration by inflammatory cells. This agent may also inhibit tumor angiogenesis.
  • Acivicin - A modified amino acid and structural analog of glutamine. Acivicin inhibits glutamine amidotransferases in the purine and pyrimidine biosynthetic pathways, thereby inhibiting tumor growth in cell lines dependent on glutamine metabolism.
  • Aclacinomycin b - An antineoplastic oligosaccharide anthracycline antibiotic isolated from the bacterium Streptomyces galilaeus. Aclacinomycin B intercalates into DNA and inhibits both the topoisomerase I and II enzymes, thereby inhibiting DNA replication and ultimately, interfering with RNA and protein synthesis.
  • Aclarubicin - An oligosaccharide anthracycline antineoplastic antibiotic isolated from the bacterium Streptomyces galilaeus. Aclarubicin intercalates into DNA and interacts with topoisomerases I and II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. Aclarubicin is antagonistic to other agents that inhibit topoisomerase II, such as etoposide, teniposide and amsacrine. This agent is less cardiotoxic than doxorubicin and daunorubicin.
  • Acodazole - A synthetic imidazoquinoline with antineoplastic activity. Acodazole intercalates into DNA, resulting in disruption of DNA replication. Use of this agent has been associated with significant cardiotoxicity.
  • Acodazole hydrochloride - The hydrochloride salt of acodazole, a synthetic imidazoquinoline with antineoplastic activity. Acodazole intercalates into DNA, resulting in disruption of DNA replication. Use of this agent has been associated with significant cardiotoxicity.
  • Acolbifene hydrochloride - The hydrochloride salt form of acolbifene, a fourth-generation estrogen receptor modulator (SERM) with potential lipid lowering and antineoplastic activity. Acolbifene specifically binds to estrogen receptors in responsive tissue, including liver, bone, breast, and endometrium. The resulting ligand-receptor complex is translocated to the nucleus where, depending on the tissue type, it promotes or suppresses the transcription of estrogen-regulated genes, thereby exerting its agonistic or antagonistic effects. Acolbifene acts as an estrogen antagonist in uterine and breast tissue, thereby blocking the effects of estrogen in these tissues. This may inhibit tumor cell proliferation in ER-positive tumor cells. This agent functions as an estrogen agonist in lipid metabolism, thereby decreasing total and LDL cholesterol levels. In bone, it decreases bone resorption and bone turnover and increases bone mineral density.
  • Acridine - A polycyclic aromatic dye with antineoplastic, antimicrobial and imaging activities. Acridine and its derivatives intercalate within DNA and RNA by forming hydrogen-bonds and stacking between base pairs resulting in DNA crosslinks and strand breaks. In addition, acridine and its derivatives are a potent inhibitor of topoisomerase II enzyme. This results in the inhibition of DNA and RNA synthesis, predominantly occurring during S phase of the cell cycle and ultimately leads to cell death.
  • Acridine carboxamide - A tricyclic acridine-based (or carboxamide-based) drug with dual topoisomerase inhibitor and potential antineoplastic activities. Acridine carboxamide inhibits both topoisomerases I and II and intercalates into DNA, resulting in DNA damage, the disruption of DNA repair and replication, the inhibition of RNA and protein synthesis, and cell death.
  • Acronine - A natural alkaloid with an acridine structure isolated from the bark of the plant Acronychia baueri (Australian scrub ash) with antineoplastic properties. Acronycine appears to alkylate DNA and interfere with DNA replication.
  • Actinium ac 225 lintuzumab - A radioimmunoconjugate consisting of the humanized monoclonal antibody lintuzumab conjugated to the alpha-emitting radioisotope actinium Ac 225 with potential antineoplastic activity. The monoclonal antibody moiety of actinium Ac 225 lintuzumab specifically binds to the cell surface antigen CD33 antigen, delivering a cytotoxic dose of alpha radiation to cells expressing CD33. CD33 is a cell surface antigen expressed on normal non-pluripotent hematopoietic stem cells and overexpressed on myeloid leukemia cells.
  • Actinium ac 225-fpi-1434 - A radioimmunoconjugate consisting of the humanized monoclonal antibody lintuzumab conjugated to the alpha-emitting radioisotope actinium Ac 225 with potential antineoplastic activity. The monoclonal antibody moiety of actinium Ac 225 lintuzumab specifically binds to the cell surface antigen CD33 antigen, delivering a cytotoxic dose of alpha radiation to cells expressing CD33. CD33 is a cell surface antigen expressed on normal non-pluripotent hematopoietic stem cells and overexpressed on myeloid leukemia cells.
  • Actinium ac-225 anti-psma monoclonal antibody j591 - A radioimmunoconjugate consisting of a humanized monoclonal antibody directed against prostate specific membrane antigen (PSMA) labeled with the alpha particle-emitting radioisotope actinium Ac-225, with potential antineoplastic activity. Upon administration, actinium Ac-225 anti-PSMA monoclonal antibody J591 binds to the extracellular domain of PSMA with high affinity, thereby delivering alpha radiation to PSMA expressing cells. PSMA, a type II membrane protein expressed in all types of prostatic tissues, is often overexpressed in tumor cells.
  • Actinomycin c2 - A natural analogue of actinomycin, a chromopeptide antineoplastic antibiotic isolated from the bacterial genus Streptomyces. Actinomycin C2 inhibits DNA replication as well as RNA and protein synthesis by various mechanisms including, intercalating into the minor groove of DNA and interfering with the function of topoisomerase II. In addition, actinomycin C2 appears to block the interaction between the SH2 domain of growth factor receptor-bound protein-2 (GRB2) and the Src homology 2 domain containing transforming protein 1 adaptor protein SHC, which plays a key role in the Ras signaling pathway thereby halting cellular differentiation and proliferation.
  • Actinomycin c3 - A natural analogue of actinomycin, a chromopeptide antineoplastic antibiotic isolated from the bacterial genus Streptomyces. Actinomycin C3 inhibits DNA replication as well as RNA and protein synthesis by various mechanisms such as intercalating into the minor groove of DNA and interfering with the function of topoisomerase II.
  • Actinomycin f1 - A chromopeptide antineoplastic antibiotic isolated from the bacterium Streptomyces chrysomallus. Actinomycin F1 intercalates into the minor groove of DNA and binds to topoisomerase II, leading to the inhibition of DNA replication and RNA and protein synthesis.
  • Activated marrow infiltrating lymphocytes - A preparation of cells, which consists of autologous marrow infiltrating lymphocytes (MILs), that are manipulated in vitro, with potential antitumor and immune stimulating activities. MILs are harvested from autologous bone marrow from multiple myeloma patients and, in vitro, are exposed to and activated by anti-CD3/anti-CD28 monoclonal antibodies covalently attached to super-paramagnetic microbeads. After removal of the beads and expansion of the cells in culture, the activated MILs (aMILs) are re-introduced into the patient. The aMILs possess enhanced myeloma specificity, and are able to infiltrate the tumor microenvironment and initiate tumor cell lysis. CD3 and CD28, co-stimulatory molecules expressed on the surface of T-lymphocytes, play a key role in the activation of T-cells.
  • Activin type 2b receptor fc fusion protein stm 434 - A soluble fusion protein containing the extracellular domain of the activin receptor type 2B (ACVR2B or ActRIIB) fused to a human Fc domain, with potential antineoplastic activity. Upon intravenous administration, STM 434 selectively binds to the growth factor activin A, thereby preventing its binding to and the activation of endogenous ActRIIB. This prevents activin A/ActRIIB-mediated signaling and inhibits the proliferation of activin A-overexpressing tumor cells. Activin A, a member of the transforming growth factor beta (TGF-beta) superfamily, is overexpressed in a variety of cancers and plays a key role in promoting cancer cell proliferation, migration, and survival.
  • Acyclic nucleoside phosphonate prodrug abi-1968 - A prodrug of an acyclic nucleoside phosphonate, with potential anti-viral and antineoplastic activities. Upon administration, acyclic nucleoside phosphonate prodrug ABI-1968 is taken up by viral-infected cells and converted to its active metabolite. The metabolite is incorporated into DNA chains by DNA polymerases, which results in the termination of DNA synthesis, inhibits viral replication and induces apoptosis and inhibits the proliferation of susceptible virally-infected tumor cells.
  • Ad5.SSTR/tk.rgd - An RGD-4C-modified, infectivity-enhanced, bicistronic type 5 adenovirus expressing herpes simplex virus thymidine kinase (HSV-tk) gene, a therapeutic suicide gene, and the somatostatin receptor type 2 (SSTR2) gene with potential antineoplastic activity. Modification with the double cyclic peptide RGD-4C allows the virus to bind to cellular integrins, frequently expressed on the surfaces of ovarian cancer cells, instead of the coxsackie and adenovirus (CAR) receptor, which is often nonfunctional in ovarian cancer cells. Upon intratumoral administration, Ad5.SSTR/TK.RGD transfects tumor cells and expresses the HSV-tk gene. After subsequent administration of a synthetic acyclic guanosine analogue prodrug like ganciclovir (GCV), expressed HSV-tk phosphorylates and activates the prodrug, which may result in inhibition of DNA synthesis and apoptosis in HSV-tk-expressing cancer cells. Additionally, as a bystander effect, adjacent non-transfected cells may be killed by the activated antiviral drug. SSTR2 expression allows imaging of gene transfer into tumor cells using a radiolabeled somatostatin analogue.
  • Ad5-cmv-nis - A recombinant type 5 adenovirus (Ad5), encoding the gene for the human sodium-iodide symporter (NIS) linked to the cytomegalovirus (CMV) promoter, with potential gene transfection activity. Upon intratumoral injection, Ad5-CMV-NIS is taken up by tumor cells, resulting in the cellular expression of NIS. Subsequently, orally administered iodine 131 is taken up by NIS-expressing tumor cells, which may result in the selective accumulation of a cytotoxic dose of beta and gamma radiation in non-thyroidal tumor cells, sparing adjacent normal tissue. NIS, an intrinsic membrane glycoprotein, is an ion pump that actively transports iodide into cells which concentrate iodine; in addition to thyroid epithelial cells, it is found in non-thyroidal tissues including the salivary glands, the gastric mucosa, and lactating mammary glands.
  • Ad5f35-lmp1/lmp2-transduced autologous dendritic cells - Autologous dendritic cells (DCs) transduced with the replication-deficient adenoviral vector Ad5F53 encoding the Epstein-Barr virus (EBV) transmembrane latent membrane proteins 1 and 2 (LMP1/LMP2) with potential immunostimulatory activity. Vaccination with Ad5F35-LMP1/LMP2-transduced autologous dendritic cells may stimulate a specific cytotoxic T-lymphocyte (CTL) response against LMP1- and LMP2-expressing tumor positive cells, resulting in tumor cell lysis and inhibition of tumor cell proliferation. LMP1 and LMP2 are expressed in various malignancies including nasopharyngeal cancer and EBV-positive Hodgkins disease.
  • Ad5-sge-reic/dkk-3 mtg-201 - A replication incompetent adenoviral vector type 5 (Ad5) encoding the tumor suppressor gene dickkopf-3 (DKK3; reduced expression in immortalized cells; REIC; Dickkopf WNT signaling pathway inhibitor 3), and containing the super gene expression (SGE) system, composed of the triple tandem enhancer sequences of human telomerase reverse transcriptase (hTERT), simian virus 40 (SV40) and cytomegalovirus (CMV), with potential immunostimulating and antineoplastic activities. Upon intratumoral (IT) injection and transfection of Ad5-SGE-REIC/Dkk-3 MTG-201, tumor cells express REIC/DKK3 protein. This may result in the activation of c-Jun-NH2-kinase (JNK) and ultimately lead to apoptosis via B-cell lymphoma-2 (Bcl2) suppression and caspase-3 activation. Increased expression of REIC/DKK3 in cancer cells may lead to an induction of tumor cell apoptosis and a reduction in tumor cell growth, while sparing normal, healthy cells expressing endogenous REIC/DKK3. In addition, the tumor cell killing promotes a cytotoxic T-lymphocyte (CTL)-mediated immune response, thereby further killing any remaining REIC-deficient, untransfected tumor cells. The SGE system, also called C-TSC (CMV promoter driving the triple tandem enhancer sequences of hTERT, SV40 and CMV), enhances gene expression compared to more conventional adenoviral vectors. REIC/DKK3 is expressed by healthy cells, but expression is reduced or absent in many cancer cells due to REIC/DKK3 gene defects. As REIC/DKK3 plays a key role in tumor cell apoptosis, the absence of the REIC protein in tumor cells prevents tumor cell apoptosis.
  • Ad5-survivin-transduced autologous dendritic cell vaccine - A cell-based cancer vaccine containing autologous dendritic cells (DCs) that are transduced with a replication-deficient adenovirus type 5 vector (Ad5) encoding a mutated form of the tumor-associated antigen (TAA) survivin, with potential immunostimulatory and antineoplastic activities. Upon administration, Ad5-survivin-transduced autologous DC vaccine may elicit an immune response against cancer cells expressing survivin by activating cytotoxic T-cells (CTLs). This leads to an induction of cell death in survivin-positive tumor cells. Survivin, a member of the inhibitor of apoptosis (IAP) family of proteins, may be upregulated in certain tumor cell types and plays a key role in tumor cell growth and survival.
  • Ad5-ycd/muttk(sr39)rep-adp - A second generation, replication-competent adenovirus type 5 containing a yeast cytosine deaminase(yCD)/mutant sr39 herpes simplex virus thymidine kinase fusion (yCD/mutTKsr39) gene and the 11.6 kDa adenovirus death protein (ADP) gene with potential oncolytic activity. Upon intratumoral administration and transduction of Ad5-yCD/mutTK(SR39)rep-ADP into tumor cells and subsequent expression of cytosine deaminase and viral thymidine kinase, administered prodrugs 5-fluorocytosine (5-FC) and ganciclovir are converted into their respective metabolites 5-fluorouracil (5-FU) and ganciclovir-5-monophosphate (ganciclovir-MP); 5-FU is subsequently metabolized to cytotoxic active metabolites 5-fluoroxyuridine monophosphate (F-UMP) and 5-5-fluoro-2'-deoxyuridine-5'-O-monophosphate (F-dUMP); ganciclovir-TP subsequently is converted by mammalian thymidine kinase to cytotoxic ganciclovir-triphosphate (ganciclovir -TP). Tumor cells adjacent to tumor cells transduced with this agent may be killed through a 'bystander effect'. ADP may enhance spread and oncolytic activity of replication-competent adenoviruses. In addition to its oncolytic activity, Ad5-yCD/mutTK(SR39)rep-ADP may exhibit radiosensitizing activity.
  • Ad5-ycd/muttksr39rep-hil12 - A replication-competent oncolytic adenovirus encoding the murine pro-inflammatory cytokine interleukin-12 (IL-12) gene and two suicide fusion genes, a yeast cytosine deaminase (yCD) and a mutant form of herpes simplex virus type 1 thymidine kinase (HSV-1 TKSR39), with potential immunomodulating and antineoplastic activities. Upon intratumoral administration of Ad5-yCD/mutTKSR39rep-hIL12, the adenovirus selectively infects and replicates in tumor cells, which results in direct tumor cell lysis. Synergistically, IL-12 expressed by the adenovirus may activate the immune system by promoting the activation of natural killer cells (NKs), inducing secretion of interferon-gamma (IFN-g) and inducing cytotoxic T-lymphocyte (CTL) responses against tumor cells, which may result in immune-mediated tumor cell death, inhibition of tumor cell proliferation and inhibition of tumor angiogenesis. In addition, Ad5-yCD/mutTKSR39rep-hIL12-infected cancer cells express yCD and TKSR39; upon administration of the prodrugs 5-fluorocytosine (5-FC) and valganciclovir (vGCV), the yCD and HSV-1 TKSR39 activate these prodrugs to form 5-fluorouracil (5-FU) and ganciclovir, respectively. 5-FU gets converted to 5-fluoro-uridine monophosphate (5-FUMP) and subsequently to 5-fluoro-deoxyuridine monophosphate (5-FdUMP); 5-FdUMP irreversible inhibits thymidylate synthase, inhibits deoxythymidine triphosphate (dTTP) formation and halts DNA synthesis. Once phosphorylated intracellularly, ganciclovir triphosphate competitively inhibits deoxyguanosine triphosphate (dGTP) incorporation into DNA and inhibits DNA synthesis.
  • Adagloxad simolenin - A carbohydrate-based immunostimulant comprised of the Globo H hexasaccharide 1 (Globo H) epitope linked to the immunostimulant carrier protein keyhole limpet hemocyanin (KLH), with potential antineoplastic activity. Upon administration of adagloxad simolenin, the carbohydrate antigen Globo H may stimulate a cytotoxic T-lymphocyte (CTL) response against Globo H-expressing tumor cells, thereby decreasing tumor cell proliferation. Globo H is a tumor associated antigen (TAA) commonly found on a variety of tumor cells including breast cancer cells. KLH improves antigenic immune recognition and T-cell responses.
  • Adavosertib - A small molecule inhibitor of the tyrosine kinase WEE1 with potential antineoplastic sensitizing activity. Adavosertib selectively targets and inhibits WEE1, a tyrosine kinase that phosphorylates cyclin-dependent kinase 1 (CDK1, CDC2) to inactivate the CDC2/cyclin B complex. Inhibition of WEE1 activity prevents the phosphorylation of CDC2 and impairs the G2 DNA damage checkpoint. This may lead to apoptosis upon treatment with DNA damaging chemotherapeutic agents. Unlike normal cells, most p53 deficient or mutated human cancers lack the G1 checkpoint as p53 is the key regulator of the G1 checkpoint and these cells rely on the G2 checkpoint for DNA repair to damaged cells. Annulment of the G2 checkpoint may therefore make p53 deficient tumor cells more vulnerable to antineoplastic agents and enhance their cytotoxic effect.
  • Adecatumumab - A recombinant human IgG1 monoclonal antibody (MoAb) directed against the tumor associated antigen (TAA) epithelial cell adhesion molecule (EpCAM) with potential antitumor activity. Adecatumumab binds to EpCAM, which may result in antibody-dependent cellular cytotoxicity (ADCC) directed against EpCAM-expressing tumor cells. EpCAM (CD326), a cell surface protein upregulated on many tumor cell types, promotes the proliferation, migration and invasiveness of tumor cells; for some cancers, overexpression has been correlated with decreased survival.
  • Adenosine a2a receptor antagonist cs3005 - An orally bioavailable immune checkpoint inhibitor and antagonist of the adenosine A2A receptor (A2AR; ADORA2A), with potential immunomodulating and antineoplastic activities. Upon administration, A2AR antagonist CS3005 selectively binds to and inhibits A2AR expressed on T-lymphocytes. This prevents tumor-released adenosine from interacting with the A2A receptors, thereby blocking the adenosine/A2AR-mediated inhibition of T-lymphocytes. This results in the proliferation and activation of T-lymphocytes, and stimulates a T-cell-mediated immune response against tumor cells. A2AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of T-cells and, upon activation by adenosine, inhibits their proliferation and activation. Adenosine is often overproduced by cancer cells and plays a key role in immunosuppression.
  • Adenosine a2a receptor antagonist nir178 - An orally bioavailable immune checkpoint inhibitor and antagonist of the adenosine A2A receptor (A2AR; ADORA2A), with potential immunomodulating and antineoplastic activities. Upon administration, A2AR antagonist NIR178 selectively binds to and inhibits A2AR expressed on T-lymphocytes. This prevents tumor-released adenosine from interacting with the A2A receptors, thereby blocking the adenosine/A2AR-mediated inhibition of T-lymphocytes. This results in the proliferation and activation of T-lymphocytes, and stimulates a T-cell-mediated immune response against tumor cells. A2AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of T-cells and, upon activation by adenosine, inhibits their proliferation and activation. Adenosine is often overproduced by cancer cells and plays a key role in immunosuppression.
  • Adenosine a2a receptor antagonist/phosphodiesterase 10a pbf-999 - An orally bioavailable inhibitor of both the adenosine A2A receptor (A2AR; ADORA2A) and phosphodiesterase 10A (PDE-10A), with potential immunomodulating and antineoplastic activities. Upon administration, A2A/PDE-10A inhibitor PBF-999 selectively binds to and inhibits A2AR expressed on T-lymphocytes. This blocks tumor-released adenosine from interacting with A2AR and prevents the adenosine/A2AR-mediated inhibition of T-lymphocytes. This results in the proliferation and activation of T-lymphocytes and stimulates a T-cell-mediated immune response against tumor cells. A2AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of T-cells and, upon activation by adenosine, inhibits T-cell proliferation and activation. Adenosine is often overproduced by cancer cells and plays a key role in immunosuppression. In addition, PBF-999 binds to and inhibits the activity of PDE-10A, thereby preventing the degradation of cyclic guanosine monophosphate (cGMP) and activates cGMP/cGMP-dependent protein kinase G (PKG) signaling. This induces beta-catenin degradation and thereby prevents the translocation of beta-catenin into the nucleus, and the beta-catenin-mediated induction of transcription of survival proteins, such as cyclin D1 and survivin. It also suppresses RAS/RAF/mitogen-activated protein kinase (MAPK) signaling. This induces apoptosis and inhibits the growth of tumor cells in which PDE-10A is overexpressed. PDE-10A is a cGMP-degrading PDE isozyme that is highly expressed in the brain and overexpressed in certain types of tumor cells. Elevation of intracellular cGMP is known to inhibit tumor proliferation and induce apoptosis. cGMP levels are low in cancer cells resulting from the overexpression PDE-10A.
  • Adenosine a2a/a2b receptor antagonist ab928 - An orally bioavailable antagonist of both the immunomodulatory checkpoint molecules adenosine A2A receptor (A2AR; ADORA2A) and A2B receptor (A2BR; ADORA2B), with potential immunomodulating and antineoplastic activities. Upon administration, A2AR/A2BR antagonist AB928 competes with tumor-released adenosine for binding to A2AR and A2BR expressed on numerous intra-tumoral immune cells, such as dendritic cells (DCs), natural killer (NK) cells, macrophages and T-lymphocytes. The binding of AB928 to A2AR and A2BR inhibits A2AR/A2BR activity and prevents adenosine-A2AR/A2BR-mediated signaling. A2AR/A2BR inhibition activates and enhances the proliferation of various immune cells, abrogates the adenosine-mediated immunosuppression in the tumor microenvironment (TME) and activates the immune system to exert anti-tumor immune responses against cancer cells, which leads to tumor cell killing. A2AR and A2BR, G protein-coupled signaling receptors, are expressed on the cell surfaces of numerous immune cells. Adenosine is often overproduced by tumor cells and plays a key role in immunosuppression and tumor cell proliferation.
  • Adenosine a2b receptor antagonist pbf-1129 - An orally bioavailable antagonist of the immunomodulatory checkpoint molecule adenosine A2B receptor (A2BR; ADORA2B), with potential anti-inflammatory, immunomodulating and antineoplastic activities. Upon administration, A2BR antagonist PBF-1129 competes with adenosine for binding to A2BR expressed on various cancer cell types and numerous immune cells, such as dendritic cells (DCs), mast cells, macrophages and lymphocytes. This inhibits A2BR activity and prevents adenosine/A2BR-mediated signaling. The inhibition of A2BR in cancer cells prevents activation of downstream oncogenic pathways, which leads to an inhibition of cell proliferation and metastasis. A2BR inhibition also prevents the release of various growth factors, cytokines and chemokines, such as vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) and angiopoietin-2 (Ang2) from immune cells, which may abrogate the adenosine-mediated immunosuppression in the tumor microenvironment (TME) and activate the immune system to exert anti-tumor immune responses against cancer cells leading to tumor cell killing. In addition, under non-cancerous inflammatory conditions, inhibition of A2BR leads to reduced activation and proliferation of various immune cells, which results in decreased pro-inflammatory cytokine production and may prevent inflammation. A2BR, a G protein-coupled signaling receptor, is expressed on the cell surfaces of numerous immune cells and is often overexpressed on a variety of cancer cell types; it plays a key role in their proliferation, progression and metastasis. Adenosine is overproduced under inflammatory conditions and plays a key role in pro-inflammatory actions. Adenosine is often overproduced by tumor cells and plays a key role in immunosuppression and tumor cell proliferation. The pro- and anti-inflammatory effects of adenosine and A2BR are cell type-specific and dependent on the extracellular microenvironment.
  • Adenovector encoding mda7 - A nonreplicating adenoviral vector (adenovector) encoding the melanoma differentiation-associated 7 gene (MDA7) with potential antineoplastic activity. After intratumoral injection and adenovector-mediated gene transfer of MDA7 into tumor cells, the expressed MDA7 transgene may inhibit tumor cell proliferation and induce tumor cell apoptosis.
  • Adenovector-transduced ap1903-inducible myd88/cd40-expressing autologous psma-specific prostate cancer vaccine bpx-201 - A genetically-modified, dendritic cell-based (DCs) vaccine in which the autologous cells are transduced with an adenoviral vector expressing the tumor antigen prostate-specific membrane antigen (PSMA) and a fusion protein composed of synthetic ligand inducible adjuvant iMC composed of a drug-inducible costimulatory CD40 receptor (iCD40) and the adaptor protein MyD88, with potential immunomodulating and antineoplastic activities. The iCD40 contains a membrane-localized cytoplasmic CD40 domain fused to the FK506 modified drug-binding protein 12 (FKBP12). Upon intradermal administration of BPX-201, these DCs accumulate in local draining lymph nodes. Twenty-four hours after vaccination, the dimerizing agent AP1903 is administered. AP1903 binds to the drug binding domain, leading to iMC oligomerization and activation of iCD40 and MyD88-mediated signaling in iMC-expressing DCs. This signaling pathway activates the DCs and stimulates a cytotoxic T-lymphocyte (CTL) response against host tumor cells that express PSMA. PSMA, a glycoprotein secreted by prostatic epithelial and ductal cells, is overexpressed in prostate cancer cells and is used as a tumor marker for both diagnosis and treatment evaluation. MyD88 is involved in interleukin 1 receptor (IL1R) and toll-like receptor (TLR) signaling.
  • Adenoviral brachyury vaccine etbx-051 - A therapeutic cancer vaccine composed of a replication-defective, serotype 5 adenovirus (Ad5) with the viral genes early 1 (E1), early 2b (E2b), and early 3 (E3) deleted, and the human transcription factor brachyury encoded, with potential immunostimulating and antineoplastic activities. Upon subcutaneous administration, the adenoviral brachyury vaccine ETBX-051 expresses the brachyury protein. The expressed brachyury may induce a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells expressing brachyury, thereby resulting in both immune-mediated inhibition of tumor cell proliferation and tumor cell death. Deletion of the E1, E2b and E3 genes from Ad5 prevents anti-adenovirus immune responses. Brachyury, a tumor-associated antigen (TAA) and member of the T-box family of transcription factors, is overexpressed in a variety of tumor types. It plays an important role in cancer progression and metastasis.
  • Adenoviral cancer vaccine pf-06936308 - A cancer vaccine composed of a replication-defective E1-deleted adenovirus vector based on chimpanzee adenovirus serotype 68 (AdC68) expressing three not yet disclosed tumor-associated antigens (TAAs), with potential immunostimulating and antineoplastic activities. Upon vaccination with the adenoviral cancer vaccine PF-06936308, the adenovirus infects cells and expresses the TAAs. In turn, the TAAs activate the immune system to produce a cytotoxic T-lymphocyte (CTL) response against cells expressing the TAAs.
  • Adenoviral muc1 vaccine etbx-061 - A therapeutic cancer vaccine composed of a replication-defective, serotype 5 adenovirus (Ad5) with the viral genes early 1 (E1), early 2b (E2b), and early 3 (E3) deleted, and the human glycoprotein mucin 1 (MUC1) encoded, with potential immunostimulating and antineoplastic activities. Upon subcutaneous administration, the adenoviral MUC1 vaccine ETBX-061 expresses the MUC1 protein. The expressed MUC1 may induce a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells expressing MUC1, thereby resulting in both immune-mediated inhibition of tumor cell proliferation and tumor cell death. Deletion of the E1, E2b and E3 genes from Ad5 prevents anti-adenovirus immune responses. MUC1, a tumor-associated antigen (TAA) and type I transmembrane protein, is overexpressed in a variety of tumor types. It plays an important role in cancer progression and metastasis.
  • Adenoviral transduced hil-12-expressing autologous dendritic cells inxn-3001 plus activator ligand inxn-1001 - Autologous dendritic cells tranduced with a replication incompetent adenovirus encoding human pro-inflammatory cytokine interleukin-12 (IL-12) (INXN-3001) in combination with the proprietary orally bioavailable, small molecule activator ligand INXN-1001, with potential immunomodulating and antineoplastic activities. Production of IL-12 is controlled by an inducible DNA element that allows transcription initiation only in the presence of the ligand inducer INXN-1001. Upon intratumoral injection of INXN-3001 and subsequent oral administration of activator ligand, INXN-1001 is able to induce expression of IL-12 in INXN-3001. IL-12 expressed by the adenovirus may activate the immune system by promoting the activation of natural killer cells, inducing the secretion of interferon-gamma and inducing a cytotoxic T lymphocyte response against tumor cells, which may result in immune-mediated tumor cell death and inhibition of tumor cell proliferation. As INXN-1001 regulates both the timing and the levels of IL-12 expression, IL-12 toxicity can be reduced.
  • Adenoviral tumor-specific neoantigen priming vaccine gad-209-fsp - An off-the-shelf neoantigen priming vaccine comprised of a great ape adenovirus (GAd) encoding tumor-specific neoantigens (TSNAs) derived from as of yet undisclosed frameshift peptides (FSPs) with potential immunostimulatory and antineoplastic activities. Upon intramuscular administration of the adenoviral tumor-specific neoantigen priming vaccine GAd-209-FSP, the adenovirus infects cells and expresses the TSNAs. This stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the TSNAs, leading to tumor cell lysis. Adenoviral-TSNA priming vaccine GAd-209-FSP is followed by boosting with a vaccine that encodes the same target TSNAs.
  • Adenoviral tumor-specific neoantigen priming vaccine grt-c901 - A personalized cancer vaccine comprised of a chimpanzee adenovirus vector (ChAdV) encoding twenty tumor-specific neoantigens (TSNAs) that have been identified through genetic sequencing of a patient's tumor cells, with potential immunostimulatory and antineoplastic activities. Upon intramuscular administration of the adenoviral-TSNA priming vaccine GRT-C901, the adenovirus infects cells and expresses the TSNAs. This stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the TSNAs, leading to tumor cell lysis. Adenoviral-TSNA vaccine GRT-C901 is followed by monthly boosting with a self-amplifying mRNA (SAM) boosting vaccine that encodes the same 20 target TSNAs. The combined immunotherapy product, consisting of priming and boosting vaccines, is referred to as GRANITE-001.
  • Adenoviral vector ad5-cea(6d) vaccine - A replication-defective, E1- and E2b-deleted oncolytic adenoviral serotype 5 (Ad5) encoding an epitope of human carcinoembryonic antigen (CEA) with potential antineoplastic activity. Adenoviral vector Ad5-CEA(6D) vaccine expresses a highly immunogenic analogue of CEA [CAP1-(6D)]. Upon administration, this vaccine may induce both humoral and cellular immune responses against tumor cells expressing the CEA antigen, thereby resulting in the immune-mediated inhibition of tumor cell proliferation and tumor cell death. CEA, a tumor-associated antigen, is overexpressed in various tumor cell types. Deletion of early genes E1 and E2b in Ad5 potentially circumvent pre-existing anti-adenovirus immunity and is capable of inducing strong immune responses.
  • Adenoviral vector encoding vegf-c lx-1101 - A genetically engineered, replication-deficient adenovirus carrying the gene encoding for the human vascular endothelial growth factor C (VEGFC; VEGF-C; Flt4 ligand), with potential pro-angiogenic activity. Upon perinodal administration of the AdAptVEGF-C adenoviral vector LX-1101, the adenovirus infects cells and promotes expression of VEGF-C. In turn, VEGF-C induces vascular and lymphatic endothelial cell proliferation locally, and may help re-grow the lymphatic system and improve symptoms associated with lymphedema (LE). VEGF-C, a lymphatic growth factor, plays a key role in (lymph)angiogenesis and the functioning of the lymphatic system.
  • Adenovirus 5/f35-human guanylyl cyclase c-padre - A recombinant adenoviral serotype 5 (Ad5) in which the Ad5-based vector fiber is replaced by the fiber from the human B adenovirus serotype 35 (F35), encoding for the human guanylyl cyclase C (hGCC), and fused to the synthetic Pan DR epitope (PADRE), with potential antineoplastic and immunomodulating activities. Upon intramuscular administration of the Ad5/F35-hGCC-PADRE, the Ad5/F35 targets CD46, which is expressed widely on most tumor cells, and the virus is taken up by cells. Once inside the cells, the virus expresses hGCC. The expressed hGCC induces both humoral and cellular immune responses against tumor cells expressing the hGCC antigen. This results in the immune-mediated killing of tumor cells. The hGCC protein is normally restricted to intestinal epithelial cells but is overexpressed by metastatic colorectal tumors. PADRE is a helper T-lymphocyte epitope that is able to augment the magnitude and duration of the cytotoxic T-lymphocyte (CTL) response. The inclusion of the chimeric Ad5/F35 fiber increases viral uptake in cells through CD46.
  • Adenovirus 5-human guanylyl cyclase c-padre vaccine - A replication-defective, recombinant adenoviral serotype 5 (Ad5) encoding human guanylyl cyclase C (hGCC) and the synthetic Pan DR epitope (PADRE), with potential antineoplastic and immunomodulating activities. Upon intramuscular administration, the Ad5-hGCC-PADRE vaccine expresses hGCC, which may induce both humoral and cellular immune responses against tumor cells expressing the hGCC antigen. This results in the immune-mediated inhibition of tumor cell proliferation, and leads to tumor death. The hGCC protein is normally restricted to intestinal epithelial cells but is overexpressed by metastatic colorectal tumors. PADRE is a helper T-lymphocyte epitope that is able to augment the magnitude and duration of the cytotoxic T-lymphocyte (CTL) response.
  • Adenovirus b7-1 - A gene-viral vector complex comprised of an adenovirus vector and B7-1 gene targeting the CD80 antigen. Adenovirus B7-1 is used as a component in antineoplastic vaccines to elicit a cytotoxic T-cell response.
  • Adenovirus encoding rat her-2/neu - A replication-defective oncolytic adenovirus, encoding rat Her-2/neu (ErbB-2), with potential antineoplastic activity. Upon administration, adenovirus encoding rat HER-2/neu may induce an immune response against tumor cells expressing the HER-2/neu antigen, which may result in the immune-mediated inhibition of tumor cell proliferation and tumor cell death. Her-2/neu, a tumor-associated antigen and member of the epidermal growth factor receptor (EGFR) family of tyrosine kinases, is overexpressed in various tumor cell types.
  • Adenovirus encoding recombinant human endostatin - A replication-defective, recombinant oncolytic adenovirus encoding human endostatin with potential antineoplastic activity. Endostatin, a 20 kDa C-terminal proteolytic fragment of collagen XVIII, is an important angiogenesis inhibitor. Upon intratumoral administration, the adenovirus infects and replicates in tumor cells. The expressed endostatin may inhibit endothelial cell proliferation and angiogenesis which may result in a reduction of tumor growth.
  • Adenovirus encoding tyrosinase/mart-1/magea6-transduced autologous dendritic cell vaccine - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) transduced with a recombinant adenoviral vector encoding three full length human melanoma associated antigens (MAAs), tyrosinase, melan-A (MART-1) and the melanoma antigen A6 (MAGEA6), with potential antineoplastic activity. Upon intradermal administration, adenovirus encoding tyrosinase/MART-1/MAGEA6-transduced autologous DC vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tyrosinase/MART-1/MAGEA6-positive tumor cells, which may result in tumor cell death and decreased tumor growth. Tyrosinase, a melanoma-specific differentiation antigen, catalyzes the first step of melanin synthesis in melanocytes. Vaccination with multi-antigen modified DC may improve the efficacy of the DC immunotherapy.
  • Adenovirus expressing mutant hpv e6/e7 - A cancer vaccine comprised of a genetically engineered, replication-deficient adenovirus encoding inactive, mutant forms of the human papillomavirus (HPV) transforming proteins E6 and E7, with potential immunostimulating and antineoplastic activities. Upon administration of adenovirus expressing mutant HPV E6/E7, the adenovirus infects and expresses the E6 and E7 proteins. The expressed E6 and E7 proteins stimulate the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing HPV E6 and E7, thereby inducing tumor cell lysis. Oncoproteins E6 and E7 play a key role in the development of cervical intraepithelial neoplasia (CIN) and cervical carcinoma.
  • Adenovirus her2-transduced autologous dendritic cell vaccine - A cell-based cancer vaccine composed of autologous dendritic cells (DCs) transduced with a replication-deficient adenovirus vector encoding HER-2 with potential antineoplastic activity. Upon administration, adenovirus HER2-transduced autologous dendritic cell vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against HER-2-positive tumor cells, which may result in tumor cell death and decreased tumor growth. HER-2, a tyrosine kinase receptor for epidermal growth factor (EGF) (also known as neu and ErbB2), is overexpressed by some breast, ovarian, and gastric cancers.
  • Adenovirus serotype 26-expressing hpv16 vaccine jnj-63682918 - A prime cancer vaccine comprised of a genetically engineered, replication-deficient adenovirus serotype 26 (Ad26) encoding the oncogenic human papillomavirus 16 (HPV16), with potential immunostimulating and antineoplastic activities. Upon intramuscular administration of Ad26-expressing HPV16 vaccine JNJ-63682918, the adenovirus infects and expresses HPV16. The expressed proteins stimulate the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing HPV16 antigens, thereby inducing tumor cell lysis. HPV16 infection plays a key role in the development of a variety of cancers.
  • Adenovirus serotype 26-expressing hpv18 vaccine jnj-63682931 - A prime cancer vaccine comprised of a genetically engineered, replication-deficient adenovirus serotype 26 (Ad26) encoding the oncogenic human papillomavirus 18 (HPV18), with potential immunostimulating and antineoplastic activities. Upon intramuscular administration of Ad26-expressing HPV18 vaccine JNJ-63682931, the adenovirus infects and expresses HPV18. The expressed proteins stimulate the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing HPV18 antigens, thereby inducing tumor cell lysis. HPV18 infection plays a key role in the development of a variety of cancers.
  • Adenovirus-encoding e.coli pnp - A replication-incompetent adenovirus encoding E. coli purine nucleoside phosphorylase (Ad/PNP) used as a prodrug activating agent. Administered intratumorally, Ad/PNP expresses the enzyme PNP, which may catalyze systematically administrated fludarabine phosphate prodrug into its active form 2-fluoroadenine (F-Ade). F-Ade inhibits DNA polymerase alpha, ribonucleotide reductase and DNA primase, thereby interrupting DNA synthesis and inhibiting tumor cell growth. Localized prodrug activation provides targeted chemotherapy, thereby potentially reducing systemic side effects.
  • Adenovirus-expressing tlr5/tlr5 agonist nanoformulation m-vm3 - A nanoparticle-based formulation containing a recombinant non-replicating adenovirus (Ad) encoding toll-like receptor 5 (TLR5) and its specific ligand protein 502S, with potential antineoplastic and immunomodulating activities. Upon administration, the Ad preferentially and specifically infects cells expressing the Coxsackievirus and adenovirus receptor (CAR), which is highly expressed in certain human tumors, and expresses both TLR5 and a specific agonistic ligand in the same cell. 502S binds to and activates TLR5, thereby allowing for continuous TLR5 signaling. This stimulates dendritic cells (DCs), monocytes, macrophages and the nuclear factor-kappa B (NF-kappaB) signaling cascade. This activation results in the production of pro-inflammatory cytokines, including interferon alpha, tumor necrosis factor-alpha and the interleukins (IL), IL-1 beta, -6 and -12. This may induce a T helper cell-1 (Th1) immune response and activate a cytotoxic T-lymphocyte (CTL) response against tumor associated antigens (TAAs). TLR5, a member of the TLR family, plays a key role in the activation of innate immunity.
  • Adenovirus-mediated human interleukin-12 - A replication incompetent adenovirus encoding human pro-inflammatory cytokine interleukin-12 (IL-12) (Ad.hIL-12), with potential immunomodulating and antineoplastic activities. Upon intratumoral administration, the adenovirus selectively infects and replicates in tumor cells, which may result in tumor cell lysis. Synergistically, IL-12 expressed by the adenovirus may activate the immune system by promoting the activation of natural killer cells (NKs), inducing secretion of interferon-gamma and inducing cytotoxic T cell responses against tumor cells, which may result in immune-mediated tumor cell death and inhibition of tumor cell proliferation.
  • Adenovirus-mediated human interleukin-12 inxn-2001 plus activator ligand inxn-1001 - A replication incompetent adenovirus encoding the human pro-inflammatory cytokine interleukin-12 (IL-12) (INXN-2001) in combination with the proprietary activator ligand INXN-1001, with potential immunomodulating and antineoplastic activities. Production of IL-12 is controlled by an inducible DNA element that allows transcription initiation only in the presence of the ligand inducer. Upon intratumoral administration of INXN-2001 and oral administration of INXN-1001, INXN-1001 is able to induce expression of IL-12 from INXN-2001. IL-12 expressed by the adenovirus may activate the immune system by promoting the activation of natural killer cells (NKs), inducing secretion of interferon-gamma and inducing cytotoxic T cell responses against tumor cells, which may result in immune-mediated tumor cell death and inhibition of tumor cell proliferation.
  • Adenovirus-p53 transduced dendritic cell vaccine - A cancer vaccine consisting of autologous dendritic cells (DCs) transduced with a recombinant adenovirus encoding p53 peptide, with potential immunomodulating activity. Intradermal vaccination with adenoviral-p53 transduced dendritic cell vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing mutant p53, resulting in tumor cell lysis. p53, a tumor suppressor gene, is mutated in many tumor cells, resulting in the loss of apoptosis regulation and abnormal cell proliferation.
  • Adenovirus-psa prostate cancer vaccine - A cancer vaccine composed of a genetically engineered, replication-deficient type 5 adenovirus carrying the human prostate-specific antigen (PSA), with potential immunostimulating and antineoplastic activities. Upon subcutaneous vaccination with the adenovirus-PSA prostate cancer vaccine, the adenovirus infects cells and expresses PSA. In turn, PSA may activate the immune system and may induce a cytotoxic T-lymphocyte response against PSA-expressing tumor cells. PSA, a tumor associated antigen, is expressed by prostate epithelial cells and is overexpressed in prostate cancer.
  • Aderbasib - An orally bioavailable inhibitor of the ADAM (A Disintegrin And Metalloprotease) family of multifunctional membrane-bound proteins with potential antineoplastic activity. Aderbasib represses the metalloproteinase ""sheddase"" activities of ADAM10 and ADAM17, which may result in the inhibition of tumor cell proliferation. The metalloproteinase domains of ADAMs cleave cell surface proteins at extracellular sites proximal to the cell membrane, releasing or ""shedding"" soluble protein etcodomains from the cell surface; the disintegrin domains of these multifunctional proteins interact with various components of the extracellular matrix (ECM). ADAM10 processes particular epithelial growth factor receptor (EGFR) ligands and appears to regulate Notch signaling through the cleavage of Notch and its related ligand delta-like ligand-1 (Dll-1). ADAM17 (also known as Tumor necrosis factor-Converting Enzyme or TACE) is involved in processing tumor necrosis factor (TNF) from its membrane bound precursor to its soluble circulating form and in processing ligands for the epidermal growth factor receptor (EGFR) family.
  • Adgmcaix-transduced autologous dendritic cells - Autologous dendritic cells (DCs) transduced with a recombinant, replication-defective adenoviral vector expressing the fusion gene granulocyte-macrophage colony-stimulating factor (GM-CSF) and carbonic anhydrase IX (CA-IX or CA9) (GMCA-9), with potential immunomodulating activity. The autologous DCs are transduced ex vivo and express the GMCA-9 fusion protein on the cell surface. Upon intradermal administration of the AdGMCAIX-transduced autologous DCs back into the patient, the DCs activate the immune system to both mount a cytotoxic T lymphocyte-mediated response against tumor cells positive for the CA9 antigen, and generate memory T cells. This may result in decreased tumor growth. CA9, also known as G250, is a renal cell carcinoma (RCC)-associated antigen and a member of the carbonic anhydrase family that contains a human leukocyte antigen (HLA)-A2.1-restricted epitope; it is found in a majority of renal cell carcinomas while absent in most normal tissues. The cytokine GM-CSF enhances the immunogenicity of CA9-based DC vaccines.
  • Adh-1 - A small, cyclic pentapeptide vascular-targeting agent with potential antineoplastic and antiangiogenic activities. ADH-1 selectively and competitively binds to and blocks N-cadherin, which may result in disruption of tumor vasculature, inhibition of tumor cell growth, and the induction of tumor cell and endothelial cell apoptosis. N-cadherin, a cell- surface transmembrane glycoprotein of the cadherin superfamily of proteins involved in calcium-mediated cell-cell adhesion and signaling mechanisms; may be upregulated in some aggressive tumors and the endothelial cells and pericytes of some tumor blood vessels.
  • Ad-hcmv-flt3l - A human serotype 5, replication-defective, first generation adenoviral vector, with the viral E1a and E3 protein encoding regions deleted, which is engineered to express the soluble, immune-mediated stimulatory gene human fms-like tyrosine kinase 3 ligand (Flt3L), under the transcriptional control of the CMV promoter, with potential immunostimulating activity. Upon administration, Ad-hCMV-Flt3L is transduced into tumor cells and Flt3L is expressed. Flt3L stimulates both the proliferation of dendritic cells (DCs) and their migration to the tumor site. Upon exposure to the tumor-associated antigens (TAA) released from dying glioma cells, which were killed by thymidine kinase-mediated valacyclovir-induced tumor cell death, the DCs initiate a specific immune response against any remaining TAA-expressing tumor cells. Flt3L is a hematopoietic growth factor and ligand for the Flt3 tyrosine kinase receptor.
  • Ad-hcmv-tk - A human serotype 5, replication-defective, first generation adenoviral vector, with the viral E1a and E3 protein encoding regions deleted, which is engineered to express the herpes simplex virus thymidine kinase (HSV-tk) gene under the transcriptional control of the CMV promoter. This agent, when administered in conjunction with a synthetic acyclic guanosine analogue, possesses potential antineoplastic activity. Upon administration into the peritumoral region after tumor resection, adenoviral vector encoding HSV thymidine kinase is transduced into tumor cells, and HSV-tk is expressed. Tumor cells expressing HSV-tk are sensitive to synthetic acyclic guanosine analogues. Subsequent administration of a synthetic acyclic guanosine analogue, such as valacyclovir (VCV) or ganciclovir (GCV), kills the tumor cells expressing HSV-tk. The release of tumor-associated antigens (TAA) by dying tumor cells may then stimulate an antitumor cytotoxic T lymphocyte (CTL) response, directed aganst any remaining tumor cells.
  • Ad-isf35 - A replication-defective adenovirus vector (Ad-ISF35), which encodes a membrane-stabilized, chimeric human-mouse CD40 binding protein (CD40 ligand; CD40L; CD154), with potential immunomodulatory and antineoplastic activities. Upon intratumoral administration, Ad-ISF135 preferentially transduces tumor cells and immunoregulatory cells in the tumor microenvironment. This increases the expression of CD154 in tumor cells, activates CD40 and stimulates signaling and immunoactivation, which are both mediated by CD40. This increases the expression of co-stimulatory molecules on these cells, which enhances their ability to function as antigen presenting cells (APCs) and increases their apoptotic potential. This leads to an increase in the infiltration of macrophages and neutrophils, which promote direct cytotoxicity, enhances the production of pro-inflammatory cytokines in the tumor microenvironment, and induces a specific cytotoxic T-lymphocyte (CTL) response against the tumor cells. In addition, transduction with Ad-ISF35 induces direct tumor cell death, probably through an anti-viral immune response. Ad-ISF35 also exerts a strong bystander effect in non-transduced cells thereby further inducing tumor cell death. Altogether, this will eradicate tumor cells. CD154, the main ligand for CD40, plays a key role in the activation of APCs, promotes immunoactivation, and increases apoptotic potential. The protein encoded by Ad-ISF35 does not contain the mouse antibody binding domains and does not induce human neutralizing antibodies. The metalloprotease cleavage site is deleted in this chimeric CD154 and thus it resists cleavage; the encoded protein also contains amino acid substitutions within the carboxy-terminal. Both sets of engineered mutations promote cell surface expression.
  • Ad-rts-hil-12 - An inducible adenoviral vector encoding human pro-inflammatory cytokine interleukin-12 (IL-12; IL12), which is under the transcriptional control of the RheoSwitch Therapeutic System (RTS) (Ad-RTS-hIL-12), with potential immunomodulating and antineoplastic activities. RTS consists of two fusion proteins: Gal4-EcR, which contains a modified ecdysone receptor (EcR) fused with the DNA binding domain of the yeast Gal4 transcription factor, and VP16-RXR, which contains a chimeric retinoid X receptor (RXR) fused with the transcription activation domain of the viral protein VP16 of herpes simplex virus type 1 (HSV1). Upon intratumoral administration of Ad-RTS-hIL-12, given in combination with the proprietary, diacylhydrazine-based activator ligand veledimex (INXN-1001), veledimex binds specifically to the EcR part of the RTS and stabilizes heterodimerization between the two fusion proteins, forming an active transcription factor, which induces the transcription of IL-12 under the control of an inducible promoter containing Gal4-binding sites. The expressed IL-12 activates the immune system by promoting the activation of natural killer cells (NK cells), inducing secretion of interferon-gamma (IFN-g) and inducing cytotoxic T-lymphocyte (CTL)-mediated responses against tumor cells, which may result in immune-mediated tumor cell lysis and inhibition of tumor cell proliferation. In the presence of veledimex, the protein heterodimer changes to a stable conformation and can bind to the inducible promoter, while without veledimex the two fusion proteins form unstable heterodimers; this allows the controlled, regulated intratumoral expression of the IL-12 gene.
  • Adrtvp-1-transduced prostate cancer cell-based vaccine - A cell-based vaccine comprised of prostate cancer cells transduced with an adenoviral vector encoding human RTVP-1 (AdRTVP-1), with potential antineoplastic and immunostimulating activities. RTVP-1, also referred to as glioma pathogenesis-related protein 1 (GLIP1), is down-regulated in prostate tumors. Regulated by tumor suppressor p53, the expression of RTVP-1 functions as a tumor suppressor, and is abundant in normal human prostate epithelial cells as well as in differentiated macrophages. Administration of this vaccine leads to an induction of apoptosis through the expression of RTVP-1 and results in a reduction in cellular proliferation in prostate cancer cells. In addition, this cancer-cell based vaccine may induce a cytotoxic T lymphocyte (CTL) response against prostate specific tumor associated antigens, resulting in an immune-mediated prostate cancer cell death. Furthermore, RTVP-1 stimulates CTL and natural killer (NK) cell activities.
  • Ad-sig-hmuc-1/ecdcd40l vaccine - A cancer vaccine consisting of a recombinant adenoviral vector encoding the tumor-associated antigen (TAA) human MUC-1 (hMUC-1) linked to the extracellular domain (ecd) of the co-stimulatory molecule CD40 ligand (CD40L) and an adenovirus signal sequence that encodes a secretory signal peptide (Ad-sig) with potential immunostimulating and antineoplastic activities. Due to the presence of the secretory signal peptide expressed by Ad-sig in the vaccine construct, transfected cells may secrete a fusion protein composed of hMUC-1 and the CD40L ecd. The CD40L moiety part of the fusion protein binds to CD40 receptors on dendritic cells (DCs). Subsequently, DCs may be activated and migrate, T-cells may expand, and a cytotoxic T lymphocyte (CTL) response against tumor cells that overexpress hMUC-1 may follow. MUC-1 is a hypoglycosylated TAA overexpressed by epithelial cancer cells.
  • Ae37 peptide/gm-csf vaccine - A vaccine containing HER2/Neu-derived epitope (amino acids 776-790) linked to li-Key peptide (li-Key/HER2/neu hybrid peptide or AE37), and combined with granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential antineoplastic and immunoadjuvant activities. Upon vaccination, AE37 may activate the immune system and stimulate T-helper cells against HER2/Neu expressing cancer cells. GM-CSF may potentiate the immune response against cancer cells expressing the HER2/Neu antigen. The Ii-Key moiety, a 4-amino acid (LRMK) epitope from the MHC class II-associated invariant chain (Ii protein), increases T-helper cell stimulation against HER2/neu antigen when compared to unmodified class II epitopes. HER2/neu, a tumor associated antigen (TAA), is overexpressed in a variety of tumor cell types and is highly immunogenic.
  • Aerosol gemcitabine - An aerosol inhalation formulation containing gemcitabine (GCB), a broad-spectrum antimetabolite and deoxycytidine analogue, with potential antineoplastic activity. Upon inhalation via a nebulizer, GCB is converted intracellularly by deoxycytidine kinase to its active metabolites difluorodeoxycytidine di- and triphosphate (dFdCDP, dFdCTP). dFdCDP inhibits ribonucleotide reductase (RNR), thereby decreasing the deoxynucleotide pool available for DNA synthesis; dFdCTP competes with deoxycytidine triphosphate (dCTP) and is incorporated into DNA, resulting in DNA strand termination and the induction of apoptosis of lung tumor cells. GCB administration directly into the lungs via aerosol yields higher concentrations of GCB locally than can be achieved by systemic GCB administration, potentially reducing systemic toxicity.
  • Aerosolized aldesleukin - An aerosol formulation of aldesleukin, a recombinant form of interleukin-2 (IL-2), with potential immunostimulating activity. Upon IL-2 inhalation, this cytokine activates lymphokine-activated killer cells and natural killer cells, and induces expression of cytotoxic cytokines, such as interferon-gamma and transforming growth factor-beta. This may eventually halt tumor cell growth. Localized administration of IL-2 may decrease toxicity and increase efficacy.
  • Aerosolized liposomal rubitecan - An aerosolized liposomal preparation of rubitecan, a water-insoluble derivative of camptothecin with potential antineoplastic activity. Rubitecan (or 9-nitro-20 (S)-camptothecin) and its active metabolite 9-aminocamptothecin (9-AC) selectively stabilize topoisomerase I-DNA covalent complexes during S-phase, 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. This agent is formulated with dilauroylphosphatidylcholine and nebulized in particle sizes of 1.2-1.6 micrometer mass median aerodynamic diameter.
  • Afatinib - An orally bioavailable anilino-quinazoline derivative and inhibitor of the receptor tyrosine kinase (RTK) epidermal growth factor receptor (ErbB; EGFR) family, with antineoplastic activity. Upon administration, afatinib selectively and irreversibly binds to and inhibits the epidermal growth factor receptors 1 (ErbB1; EGFR), 2 (ErbB2; HER2), and 4 (ErbB4; HER4), and certain EGFR mutants, including those caused by EGFR exon 19 deletion mutations or exon 21 (L858R) mutations. This may result in the inhibition of tumor growth and angiogenesis in tumor cells overexpressing these RTKs. Additionally, afatinib inhibits the EGFR T790M gatekeeper mutation which is resistant to treatment with first-generation EGFR inhibitors. EGFR, HER2 and HER4 are RTKs that belong to the EGFR superfamily; they play major roles in both tumor cell proliferation and tumor vascularization and are overexpressed in many cancer cell types.
  • Afatinib dimaleate - The dimaleate salt form of afatinib, an orally bioavailable anilino-quinazoline derivative and inhibitor of the receptor tyrosine kinase (RTK) epidermal growth factor receptor (ErbB; EGFR) family, with antineoplastic activity. Upon administration, afatinib selectively and irreversibly binds to and inhibits the epidermal growth factor receptors 1 (ErbB1; EGFR), 2 (ErbB2; HER2), and 4 (ErbB4; HER4), and certain EGFR mutants, including those caused by EGFR exon 19 deletion mutations or exon 21 (L858R) mutations. This may result in the inhibition of tumor growth and angiogenesis in tumor cells overexpressing these RTKs. Additionally, afatinib inhibits the EGFR T790M gatekeeper mutation which is resistant to treatment with first-generation EGFR inhibitors. EGFR, HER2 and HER4 are RTKs that belong to the EGFR superfamily; they play major roles in both tumor cell proliferation and tumor vascularization and are overexpressed in many cancer cell types.
  • Afimoxifene - A tamoxifen metabolite with both estrogenic and anti-estrogenic effects. Afimoxifene has a higher affinity for the estrogen receptor than tamoxifen, and functions as an antagonist in breast cancer cells.
  • Afp gene hepatocellular carcinoma vaccine - A cancer vaccine composed of naked plasmid DNA of the gene for the tumor-associated antigen alpha-fetoprotein (AFP), a macromolecule that acts as a specific immunologic target for hepatocellular carcinoma. This agent exerts an antitumor effect by inducing cytotoxic T-lymphocytes to attack AFP-expressing tumor cells.
  • Afuresertib - An orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Afuresertib binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
  • Agaricus blazei murill extract - A dietary supplement containing an extract of the Basidiomycete fungus Agaricus blazei Murill with potential chemopreventive, antineoplastic and immunopotentiating activities. Agaricus blazei Murill extract contains high levels of phytochemicals, especially beta-D-glucans. Beta-D-glucans may promote dendritic cell (DC) maturation; increase interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha) and immunoglobulin levels; and may enhance natural killer (NK) cell activity, potentially boosting anti-tumor host immune responses.
  • Agatolimod sodium - The tricosasodium salt of a synthetic 24-mer oligonucleotide containing 3 CpG motifs with potential antineoplastic and immunostimulatory activity. Agatolimod selectively targets Toll-like receptor 9 (TLR9), thereby activating dendritic and B cells and stimulating cytotoxic T cell and antibody responses against tumor cells bearing tumor antigens.
  • Agerafenib - An orally available v-raf murine sarcoma viral oncogene homolog B1 (B-raf) serine/threonine protein kinase inhibitor with potential antineoplastic activity. Agerafenib specifically and selectively inhibits the activity of the mutated form (V600E) of B-raf kinase. This inhibits the activation of the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) signaling pathway and may result in a decrease in the proliferation of tumor cells expressing the mutated B-raf gene. The Raf mutation BRAF V600E, in which valine is substituted for glutamic acid at residue 600, is frequently found in a variety of human tumors and results in the constitutive activation of the RAF/MEK/ERK signaling pathway that regulates cellular proliferation and survival.
  • Aglatimagene besadenovec - An adenoviral vector engineered to express the herpes simplex virus thymidine kinase (HSV-tk) gene, which, when administered in conjunction with a synthetic acyclic guanosine analogue, possesses potential antineoplastic activity. Aglatimagene besadenovec is transduced into tumor cells, sensitizing tumor cells that overexpress HSV-tk to synthetic acyclic guanosine analogues. Subsequently, a low dose of a synthetic acyclic guanosine analogue such as valacyclovir (VCV) or ganciclovir (GCV) is given, which may preferentially kill tumor cells containing the adenoviral vector and overexpressing HSV-tk. Release of tumor-associated antigens (TAAs) by dying tumor cells may then stimulate an antitumor cytotoxic T lymphocyte (CTL) response.
  • Agonistic anti-ox40 monoclonal antibody incagn01949 - An agonistic human immunoglobulin G1 (IgG1) monoclonal antibody that recognizes the co-stimulatory receptor OX40 (CD134; TNFRSF4), with potential immunostimulatory and antineoplastic activities. Upon administration, agonistic anti-OX40 monoclonal antibody INCAGN01949 selectively binds to and activates OX40 on activated T-cells, thereby potentiating T-cell receptor (TCR) signaling. OX40 activation inhibits regulatory T-cell (Treg)-mediated suppression of effector T-cells, induces the proliferation of memory and effector T-lymphocytes and modulates cytokine production. In the presence of tumor-associated antigens (TAAs), this may promote an immune response against the TAA-expressing tumor cells. In addition, the IgG1 Fc region of INCAGN01949 binds to and co-engages with the IgG Fc-gamma receptor III (FcgammaRIII; CD16) expressed by immune effector cells; thus, binding activates FcgammaRIII-mediated signaling and facilitates the selective depletion of intratumoral Tregs, thereby further enhancing the cytotoxic T-lymphocyte (CTL)-mediated tumor cell response. OX40, a cell surface glycoprotein and member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on T-lymphocytes and provides a co-stimulatory signal for the proliferation and survival of activated T-cells; OX40 stimulation abrogates the immunosuppressive tumor microenvironment.
  • Agonistic anti-ox40 monoclonal antibody medi6469 - An agonistic monoclonal antibody against the co-stimulatory receptor OX40 (CD134), with potential immunostimulatory and antineoplastic activities. Upon intravenous administration, anti-OX40 monoclonal antibody MEDI6469 selectively binds to and activates OX40. OX40 activation induces proliferation of effector T-lymphocytes. In the presence of tumor-associated antigens (TAAs), this may promote an immune response against the TAA-expressing tumor cells. OX40, a cell surface glycoprotein and member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on T-lymphocytes and provides a co-stimulatory signal for the proliferation and survival of activated T-cells.
  • Aim2(-1)/ht001(-1)/taf1b(-1) frameshift peptide vaccine - A cancer vaccine containing the three frame shift peptides (FSP) AIM2(-1), HT001(-1) and TAF1B(-1), with potential immunomodulating activity. Upon administration, the AIM2(-1)/HT001(-1)/TAF1B(-1) FSP vaccine may induce an immune response against microsatellite instability (MSI) colorectal cancer-associated antigens. Frame shift mutations of AIM2 (absent in melanoma 2, an interferon-inducible protein), HT001 (asteroid homolog 1 or ASTE1, with an unknown function) and TAF1B (TATA box-binding protein-associated RNA polymerase I B, a transcription factor) are seen in MSI-positive colorectal cancers and may be associated with malignant transformation, tumor progression and the presence of tumor-infiltrating lymphocytes. These FSPs all have one-base deletions.
  • Akr1c3-activated prodrug obi-3424 - A small-molecule nitro-benzene, aldo-keto reductase 1C3 (AKR1C3)-activated prodrug of N,N'-bisethylenephosphoramidate, a DNA bis-alkylating agent, with potential antineoplastic activity. Upon intravenous administration, AKR1C3-activated prodrug OBI-3424 is converted to its active form by AKR1C3, which is upregulated in certain tumor cell types while not expressed in normal healthy cells. The active metabolite selectively binds to and alkylates DNA in AKR1C3-overexpressing tumor cells, resulting in DNA base pair mismatching, interstrand crosslinking and inhibition of DNA repair and synthesis, cell-cycle arrest, and apoptosis. As the expression of AKR1C3 is restricted to tumors, OBI-3424 is selectively converted to its active metabolite in tumor cells only while its conversion in normal, healthy tissue is absent; this allows for an increased cytotoxic effect of the alkylating agent in tumor cells while decreasing its toxicity.
  • Akt 1/2 inhibitor bay1125976 - An orally bioavailable inhibitor of the serine/threonine protein kinase AKT (protein kinase B) isoforms 1 and 2 (AKT1/2) with potential antineoplastic activity. AKT1/2 inhibitor BAY1125976 selectively binds to and inhibits the phosphorylation and activity of AKT1/2 in a non-ATP competitive manner, which may result in the inhibition of the phosphatidylinositol 3 (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. This may lead to both the reduction of cell proliferation and the induction of cell apoptosis in AKT-overexpressing tumor cells. The AKT signaling pathway is often deregulated in cancer and is associated with tumor cell proliferation, survival and migration.
  • Akt inhibitor ly2780301 - An orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Akt inhibitor LY2780301 binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway, thereby leading to inhibition of cell proliferation and the induction of apoptosis in tumor cells. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
  • Akt inhibitor mk2206 - An orally bioavailable allosteric inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Akt inhibitor MK2206 binds to and inhibits the activity of Akt in a non-ATP competitive manner, which may result in the inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
  • Akt inhibitor sr13668 - An orally bioavailable indole-3-carbinol (I3C) analogue inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic and antiangiogenic activities. Akt inhibitor SR13668 binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation, and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
  • Akt/erk inhibitor onc201 - A water soluble, orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) and extracellular signal-regulated kinase (ERK), with potential antineoplastic activity. Upon administration, Akt/ERK inhibitor ONC201 binds to and inhibits the activity of Akt and ERK, which may result in inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signal transduction pathway as well as the mitogen-activated protein kinase (MAPK)/ERK-mediated pathway. This may lead to the induction of tumor cell apoptosis mediated by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/TRAIL death receptor type 5 (DR5) signaling in AKT/ERK-overexpressing tumor cells. The PI3K/Akt signaling pathway and MAPK/ERK pathway are upregulated in a variety of tumor cell types and play a key role in tumor cell proliferation, differentiation and survival by inhibiting apoptosis. In addition, ONC201 is able to cross the blood-brain barrier.
  • Akt-1/2 inhibitor-treated tumor infiltrating lymphocytes - Autologous tumor infiltrating lymphocytes (TILs) harvested directly from the infiltrate of a patient's tumor and treated with an inhibitor of the serine/threonine kinases Akt-1 and -2 (Akti-1/2) during ex vivo expansion, with potential antineoplastic activity. Upon reintroduction into the patient, the Akti-1/2-treated TILs recognize and kill cancer cells. Akt inhibition promotes the immunologic memory of the TILs and enhances their expansion, in vivo long-term persistence and antitumor activity.

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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