C-1027

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C-1027 or Lidamycin is a antitumor antibiotic consisting of a complex of an enediyne chromophore and an apoprotein.[1][2][3][4] [5][6] It shows antibiotic activity against most Gram-positive bacteria.[7] 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.[7] 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.[8]

C-1027 Mechanism

C-1027 shows promise as an anticancer drug and is currently undergoing phase II clinical trials in China,[9] with a 30% success rate.[10] 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.[6]

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Contributors: Prab R. Tumpati, MD