C-1027

Chemical Compound
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References

C-1027 or Lidamycin is a antitumor antibiotic consisting of a complex of an enediyne chromophore and an apoprotein.<ref name="HuXue1988">,

 A new macromolecular antitumor antibiotic, C-1027. I. Discovery, taxonomy of producing organism, fermentation and biological activity., 
 The Journal of Antibiotics, 
 1988,
 Vol. 41(Issue: 11),
 pp. 1575–1579,
 DOI: 10.7164/antibiotics.41.1575,
 PMID: 3198491,</ref><ref name="OtaniMinami1988">, 
 A new macromolecular antitumor antibiotic, C-1027. II. Isolation and physico-chemical properties., 
 The Journal of Antibiotics, 
 1988,
 Vol. 41(Issue: 11),
 pp. 1580–1585,
 DOI: 10.7164/antibiotics.41.1580,
 PMID: 3198492,</ref><ref name="ZhenMing1989">, 
 A new macromolecular antitumor antibiotic, C-1027. III. Antitumor activity., 
 The Journal of Antibiotics, 
 1989,
 Vol. 42(Issue: 8),
 pp. 1294–1298,
 DOI: 10.7164/antibiotics.42.1294,
 PMID: 2759910,</ref><ref name="Ken-ichiroMinami1993">, 
 Structure and cycloaromatization of a novel enediyne, C-1027 chromophore, 
 Tetrahedron Lett., 
 1993,
 Vol. 34(Issue: 16),
 pp. 2637–2640,
 DOI: 10.1016/S0040-4039(00)77644-1,</ref>

<ref name="Liang_2010">,

 Complexity and simplicity in the biosynthesis of enediyne natural products, 
 Natural Product Reports, 
 
 Vol. 27(Issue: 4),
 pp. 499–528,
 DOI: 10.1039/b908165h,
 PMID: 20336235,</ref><ref name="Zhen_2009">, 
 Lidamycin shows highly potent cytotoxic to myeloma cells and inhibits tumor growth in mice, 
 Acta Pharmacologica Sinica, 
 
 Vol. 30(Issue: 7),
 pp. 1025–32,
 DOI: 10.1038/aps.2009.75,
 PMID: 19575006,
 PMC: 4006655,</ref> It shows antibiotic activity against most Gram-positive bacteria.<ref name="Xu_1994" /> It is one of the most potent cytotoxic molecules known, due to its induction of a higher ratio of DNA double-strand breaks than single-strand breaks.

C-1027’s chromophore contains a nine-membered enediyne that is responsible for most of the molecule’s biological activity.<ref name="Xu_1994">,

 C1027 chromophore, a potent new enediyne antitumor antibiotic, induces sequence-specific double-strand DNA cleavage, 
 Biochemistry, 
 
 Vol. 33(Issue: 19),
 pp. 5947–54,
 
 PMID: 8180224,</ref> Unlike other enediynes, this molecule contains no triggering mechanism. It is already primed to undergo the cycloaromatization reaction without external activation to produce the toxic 1,4-benzenoid diradical species. C-1027 can induce oxygen-independent interstrand DNA crosslinks in addition to the oxygen-dependent single- and double-stranded DNA breaks typically generated by other enediynes. This unique oxygen-independent mechanism suggests that C-1027 may be effective against hypoxic tumor cells.<ref>, 
 Improvement of the enediyne antitumor antibiotic C-1027 production by manipulating its biosynthetic pathway regulation in Streptomyces globisporus, 
 Journal of Natural Products, 
 
 Vol. 74(Issue: 3),
 pp. 420–4,
 DOI: 10.1021/np100825y,
 PMID: 21250756,
 PMC: 3064734,</ref>

C-1027 Mechanism

C-1027 shows promise as an anticancer drug and is currently undergoing phase II clinical trials in China,<ref>,

 Draft genome sequence of Streptomyces globisporus C-1027, which produces an antitumor antibiotic consisting of a nine-membered enediyne with a chromoprotein, 
 Journal of Bacteriology, 
 
 Vol. 194(Issue: 15),
 pp. 4144,
 DOI: 10.1128/JB.00797-12,
 PMID: 22815456,
 PMC: 3416545,</ref> with a 30% success rate.<ref>, 
 Enediynes: Exploration of microbial genomics to discover new anticancer drug leads, 
 Bioorganic & Medicinal Chemistry Letters, 
 
 Vol. 25(Issue: 1),
 pp. 9–15,
 DOI: 10.1016/j.bmcl.2014.11.019,
 PMID: 25434000,
 PMC: 4480864,</ref> It can induce apoptosis in many cancer cells and recent studies have indicated that it induces unusual DNA damage responses to double-strand breaks, including altering cell cycle progression and inducing chromosomal aberrations.<ref name="Zhen_2009" />

References

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