WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406386
Description: CGK733 is an ATM inhibitor and ATR inhibitor, which significantly enhanced taxol-induced cytotoxicity in HBV-positive HepG2.2.15 cells. The mechanism lies in CGK733 triggers the formation of multinucleated cells thus promotes the premature mitotic exit of taxol-induced mitotic-damaged cells through multinucleation and mitotic catastrophe in HBV-positive HepG2.2.15 cells. These results suggest that CGK733 could potentially reverse the taxol resistance in HBV-positive HCC cells and may suggest a novel strategy to treat HBV-infected HCC patients.
MedKoo Cat#: 406386
Chemical Formula: C23H18Cl3FN4O3S
Exact Mass: 554.01492
Molecular Weight: 555.84
Elemental Analysis: C, 49.70; H, 3.26; Cl, 19.13; F, 3.42; N, 10.08; O, 8.64; S, 5.77
Synonym: CGK733; CGK-733; CGK 733.
IUPAC/Chemical Name: 2,2-diphenyl-N-(2,2,2-trichloro-1-(3-(4-fluoro-3-nitrophenyl)thioureido)ethyl)acetamide
InChi Key: HLCDNLNLQNYZTK-UHFFFAOYSA-N
InChi Code: InChI=1S/C23H18Cl3FN4O3S/c24-23(25,26)21(30-22(35)28-16-11-12-17(27)18(13-16)31(33)34)29-20(32)19(14-7-3-1-4-8-14)15-9-5-2-6-10-15/h1-13,19,21H,(H,29,32)(H2,28,30,35)
SMILES Code: O=C(NC(NC(NC1=CC=C(F)C([N+]([O-])=O)=C1)=S)C(Cl)(Cl)Cl)C(C2=CC=CC=C2)C3=CC=CC=C3
(copied from : http://en.wikipedia.org/wiki/CGK733_fraud)
CGK733 was a synthetic chemical substance which was reported in 2006 to have remarkable properties in reversing cell senescence (aging). However, the entire work behind the discovery of this compound has since been found to be falsified and the authors of the original reports have retracted all their claims.
CGK733 was claimed to be an inhibitor of ATM/ATR kinases, which are involved in DNA damage repair. CGK was claimed to extend the lifetime of cultured cells by approximately 20 divisions, or roughly 25%, specifically in mammalian cells.
The original report garnered scientific attention, but was retracted in 2008. The retraction states that the screen to identify CGK733 as an anti-senescence agent was not carried out; experiments exploring the cellular effects of CGK733 were misrepresented; the identification of ATM as the target of CGK733 was fabricated; a compound which was essential for ATM target validation had not been synthesized; and the chemical structure of CGK733 was misrepresented. The principal investigator, Tae Kook Kim, and several associates were consequently suspended from their positions at the Korea Advanced Institute of Science & Technology.
1: Jekimovs C, Bolderson E, Suraweera A, Adams M, O'Byrne KJ, Richard DJ. Chemotherapeutic compounds targeting the DNA double-strand break repair pathways: the good, the bad, and the promising. Front Oncol. 2014 Apr 22;4:86. doi: 10.3389/fonc.2014.00086. eCollection 2014. Review. PubMed PMID: 24795863; PubMed Central PMCID: PMC4001069.
2: Tang ML, Khan MK, Croxford JL, Tan KW, Angeli V, Gasser S. The DNA damage response induces antigen presenting cell-like functions in fibroblasts. Eur J Immunol. 2014 Apr;44(4):1108-18. doi: 10.1002/eji.201343781. Epub 2014 Feb 16. PubMed PMID: 24375454.
3: Williams TM, Nyati S, Ross BD, Rehemtulla A. Molecular imaging of the ATM kinase activity. Int J Radiat Oncol Biol Phys. 2013 Aug 1;86(5):969-77. doi: 10.1016/j.ijrobp.2013.04.028. Epub 2013 May 29. PubMed PMID: 23726004; PubMed Central PMCID: PMC3710537.
4: Fallone F, Britton S, Nieto L, Salles B, Muller C. ATR controls cellular adaptation to hypoxia through positive regulation of hypoxia-inducible factor 1 (HIF-1) expression. Oncogene. 2013 Sep 12;32(37):4387-96. doi: 10.1038/onc.2012.462. Epub 2012 Oct 22. PubMed PMID: 23085754.
5: Wang H, Zuo B, Wang H, Ren L, Yang P, Zeng M, Duan D, Liu C, Li M. CGK733 enhances multinucleated cell formation and cytotoxicity induced by taxol in Chk1-deficient HBV-positive hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2012 May 25;422(1):103-8. doi: 10.1016/j.bbrc.2012.04.115. Epub 2012 Apr 30. PubMed PMID: 22564734.
6: Choi S, Toledo LI, Fernandez-Capetillo O, Bakkenist CJ. CGK733 does not inhibit ATM or ATR kinase activity in H460 human lung cancer cells. DNA Repair (Amst). 2011 Oct 10;10(10):1000-1; author reply 1002. doi: 10.1016/j.dnarep.2011.07.013. Epub 2011 Aug 23. PubMed PMID: 21865098; PubMed Central PMCID: PMC3189494.
7: Takahashi A, Mori E, Su X, Nakagawa Y, Okamoto N, Uemura H, Kondo N, Noda T, Toki A, Ejima Y, Chen DJ, Ohnishi K, Ohnishi T. ATM is the predominant kinase involved in the phosphorylation of histone H2AX after heating. J Radiat Res. 2010;51(4):417-22. Epub 2010 Apr 24. PubMed PMID: 20448412.
8: Alao JP, Sunnerhagen P. The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation. Radiat Oncol. 2009 Nov 10;4:51. doi: 10.1186/1748-717X-4-51. PubMed PMID: 19903334; PubMed Central PMCID: PMC2777912.
9: Normile D. Scientific misconduct. Science retracts discredited paper; bitter patent dispute continues. Science. 2009 Apr 24;324(5926):450-1. doi: 10.1126/science.324_450. PubMed PMID: 19390012.
10: Crescenzi E, Palumbo G, de Boer J, Brady HJ. Ataxia telangiectasia mutated and p21CIP1 modulate cell survival of drug-induced senescent tumor cells: implications for chemotherapy. Clin Cancer Res. 2008 Mar 15;14(6):1877-87. doi: 10.1158/1078-0432.CCR-07-4298. PubMed PMID: 18347191.