CDK9-IN-53

CDK9-IN-53 is a potent and selective CDK9 inhibitor with a K_i of 7 nM and an IC₅₀ of 14 nM against CDK9/Cyclin T1. CDK9-IN-53 achieves highly selective inhibition by competitively binding to the ATP pocket of CDK9, thereby blocking RNAPII transcription and downregulating the anti-apoptotic protein Mcl-1, ultimately triggering Caspase-dependent apoptosis in cancer cells. CDK9-IN-53 can be used for research on chronic lymphocytic leukemia^[1]. In Vitro:CDK9-IN-53 (compound 12u) (48 h) inhibited the proliferation of HCT-116, A2780, MCF-7, and other tumor cell lines with GI₅₀ values of 0.320-0.780 μM, whereas non-transformed HMEC-1, MRC-5, and WI-38 cells were less sensitive with GI₅₀ values of 3.120-5.960 μM^[1].
CDK9-IN-53 (GI₅₀-10 x GI₅₀; 24-48 h) significantly activates Caspase-3 activity, induces apoptosis in a dose-dependent manner, causes G2/M phase cell cycle arrest, inhibits RNAPII Ser-2 phosphorylation, downregulates Mcl-1 and HDM2 expression levels, and induces PARP cleavage in A2780 ovarian cancer cells^[1].
CDK9-IN-53 (1.0-10 μM; 8-48 h) strongly induced Caspase-3 activity and apoptosis in primary chronic lymphocytic leukemia (CLL) cells (LD₅₀ = 2.6 μM) and significantly downregulated the expression level of the anti-apoptotic protein Mcl-1^[1].
CDK9-IN-53 inhibits CDK9/cyclin T1 with IC₅₀ = 14 nM in in vitro kinase biochemical inhibition assays, and CDK9 K_i = 7 nM has been reported, showing >80-fold selectivity over CDK2^[1].