“C-1027”的意思、由来-开放百科全书

C-1027 or Lidamycin is an enediyne antitumor antibiotic.^[2] It was first isolated as an apoprotein-chromophore complex.^[3] It shows antibiotic activity against most Gram-positive bacteria.^[4] 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.^[4] 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.^[5]

C-1027 shows promise as an anticancer drug and is currently undergoing phase II clinical trials in China,^[6] with a 30% success rate.^[7] 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.^[2]

References

1. ^{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/9962646#section=Substances-by-Category|title=Lidamycin|first=|last=Pubchem|website=pubchem.ncbi.nlm.nih.gov|access-date=5 May 2018}}
2. ^¹{{cite journal | vauthors = Zhen YZ, Lin YJ, Li Y, Zhen YS | title = Lidamycin shows highly potent cytotoxic to myeloma cells and inhibits tumor growth in mice | journal = Acta Pharmacologica Sinica | volume = 30 | issue = 7 | pages = 1025–32 | date = July 2009 | pmid = 19575006 | pmc = 4006655 | doi = 10.1038/aps.2009.75 }}
3. ^{{cite journal | vauthors = Liang ZX | title = Complexity and simplicity in the biosynthesis of enediyne natural products | journal = Natural Product Reports | volume = 27 | issue = 4 | pages = 499–528 | date = April 2010 | pmid = 20336235 | doi = 10.1039/b908165h }}
4. ^¹{{cite journal | vauthors = Xu YJ, Zhen YS, Goldberg IH | title = C1027 chromophore, a potent new enediyne antitumor antibiotic, induces sequence-specific double-strand DNA cleavage | journal = Biochemistry | volume = 33 | issue = 19 | pages = 5947–54 | date = May 1994 | pmid = 8180224 }}
5. ^{{cite journal | vauthors = Chen Y, Yin M, Horsman GP, Shen B | title = Improvement of the enediyne antitumor antibiotic C-1027 production by manipulating its biosynthetic pathway regulation in Streptomyces globisporus | journal = Journal of Natural Products | volume = 74 | issue = 3 | pages = 420–4 | date = March 2011 | pmid = 21250756 | pmc = 3064734 | doi = 10.1021/np100825y }}
6. ^{{cite journal | vauthors = Wang L, Wang S, He Q, Yu T, Li Q, Hong B | title = Draft genome sequence of Streptomyces globisporus C-1027, which produces an antitumor antibiotic consisting of a nine-membered enediyne with a chromoprotein | journal = Journal of Bacteriology | volume = 194 | issue = 15 | pages = 4144 | date = August 2012 | pmid = 22815456 | pmc = 3416545 | doi = 10.1128/JB.00797-12 }}
7. ^{{cite journal | vauthors = Shen B, Yan X, Huang T, Ge H, Yang D, Teng Q, Rudolf JD, Lohman JR | title = Enediynes: Exploration of microbial genomics to discover new anticancer drug leads | journal = Bioorganic & Medicinal Chemistry Letters | volume = 25 | issue = 1 | pages = 9–15 | date = January 2015 | pmid = 25434000 | pmc = 4480864 | doi = 10.1016/j.bmcl.2014.11.019 }}