CGK733

• CAT Number: I005413
• CAS Number: 905973-89-9
• Molecular Formula: C₂₃H₁₈Cl₃FN₄O₃S
• Molecular Weight: 555.84
• Purity: ≥95%
• Target: ATM/ATR
• Solubility: 10 mM in DMSO
• Storage: Store at -20C
• InChI: 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)
• InChIKey: HLCDNLNLQNYZTK-UHFFFAOYSA-N
• SMILES: C1=CC=C(C=C1)C(C2=CC=CC=C2)C(=O)NC(C(Cl)(Cl)Cl)NC(=S)NC3=CC(=C(C=C3)F)[N+](=O)[O-]

CGK 733 is a small molecule inhibitor reportedly targeting the kinase activities of ATM and ATR.IC50 Value:Target: ATM/ATRin vitro: Culture of MCF-7 breast cancer cells with 10 μM CGK733 induced a detectable decline of cyclin D1 levels within 2 h of exposure, and this effect was maximal between 4 and 6 h after exposure, CGK733 induced the loss of cyclin D1 expression at concentrations as low as 5 μM and this activity was maximal at 10 to 20 μM The CGK733 induced attenuation of cyclin D1 levels was inhibited by the 26S proteasome inhibitor MG132 but not the GSK3β inhibitor lithium chloride (LiCl) in MCF-7 and T47D cells [1]. CGK733 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 [2].

Reference

1:CGK733-induced LC3 II formation is positively associated with the expression of cyclin-dependent kinase inhibitor p21Waf1/Cip1 through modulation of the AMPK and PERK/CHOP signaling pathways. Wang Y, Kuramitsu Y, Baron B, Kitagawa T, Tokuda K, Akada J, Nakamura K.Oncotarget. 2015 Nov 24;6(37):39692-701. doi: 10.18632/oncotarget.5625. PMID: 26486079 Free PMC Article2:PERK/CHOP contributes to the CGK733-induced vesicular calcium sequestration which is accompanied by non-apoptotic cell death. Wang Y, Kuramitsu Y, Baron B, Kitagawa T, Akada J, Tokuda K, Cui D, Nakamura K.Oncotarget. 2015 Sep 22;6(28):25252-65. doi: 10.18632/oncotarget.4487. PMID: 26259235 Free PMC Article3:CGK733 enhances multinucleated cell formation and cytotoxicity induced by taxol in Chk1-deficient HBV-positive hepatocellular carcinoma cells. Wang H, Zuo B, Wang H, Ren L, Yang P, Zeng M, Duan D, Liu C, Li M.Biochem Biophys Res Commun. 2012 May 25;422(1):103-8. doi: 10.1016/j.bbrc.2012.04.115. Epub 2012 Apr 30. PMID: 22564734 4:CGK733 does not inhibit ATM or ATR kinase activity in H460 human lung cancer cells. Choi S, Toledo LI, Fernandez-Capetillo O, Bakkenist CJ.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. No abstract available. PMID: 21865098 Free PMC Article5:The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation. Alao JP, Sunnerhagen P.Radiat Oncol. 2009 Nov 10;4:51. doi: 10.1186/1748-717X-4-51. PMID: 19903334 Free PMC Article