481724-82-7
481724-82-7 結構式
基本信息
英文別名
CGP74514AAURORA KA-7574
CGP-74514A hydrochloride (CGP74514A)
N-(CIS-2-AMINOCYCLOHEXYL)-N-(3-CHLOROPHENYL)-9-ETHYL-9H-PURINE-2,6-DIAMINE
N-[(1R,2S)-2-Aminocyclohexyl]-N'-(3-Chlorophenyl)-9-Ethylpurine-2,6-Diamine
2-N-[(1R,2S)-2-aminocyclohexyl]-6-N-(3-chlorophenyl)-9-ethylpurine-2,6-diamine:hydrochloride
9H-Purine-2,6-diamine, N2-[(1R,2S)-2-aminocyclohexyl]-N6-(3-chlorophenyl)-9-ethyl-, monohydrochloride, rel- (9CI)
應用領域
用途一
CGP74514A is a CDK1 inhibitor with potential anticancer activity. In U937 cells, CGP74514A - induced apoptosis (5 microM) became apparent within 4 hr and approached 100% by 24 hr. The pan- caspase inhibitor Boc-fmk and the caspase-8 inhibitor lETD-fmk opposed CGP74514A -induced caspase-9 activation and PARP degradation, but not cytochrome c or Smac/DIABLO release. CGP74514A -mediated apoptosis was substantially blocked by ectopic expression of full-length Bel- 2, a loop-deleted mutant Bcl-2, and Bcl-x(L). CGP74514A treatment (5 microM; 18 hr) resulted in increased p21(CIP1) expression, p27(KIP1) degradation, diminished E2F1 expression, and dephosphorylation of p34(CDC2). It also induced early (i.e., within 2 hr) inhibition of CDK1 activity and dephosphorylation of pRb, followed by pRb degradation, but did not block pRb phosphorylation at CDK2- and CDK4- specific sites. These findings indicate that the selective CDK1 inhibitor, CGP74514A , induces complex changes in cell cycle-related proteins in human leukemia cells accompanied by extensive mitochondrial damage, caspase activation, and apoptosis.