KB-0742 dihydrochloride

KB-0742 dihydrochloride is a potent, selective and orally active CDK9 inhibitor with an IC 50 of 6 nM for CDK9/cyclin T1 . KB-0742 dihydrochloride is selective for CDK9/cyclin T1 with >50-fold selectivity over other CDK kinases. KB-0742 dihydrochloride has potent anti-tumor activity

In Vitro

KB-0742 (6 hours; 0.1-10 μM; 22Rv1 cells) treatment significant reduction of downstream phosphorylation of RNA Pol II at Ser2 and Ser7, and diminished phosphorylation at Ser5. Global androgen receptor (AR)-FL and AR-V protein levels are significantly reduced starting at 6 h treatment time, which is accompanied by the reduction of phospho-AR levels (Ser81). KB-0742 (48-72 hours) treatment shows cytostatic effects in prostate cancer and leukemia cell lines. KB-0742 shows antiproliferative activity with GR 50 s of 0.183 μM and 0.288 μM for 22Rv1 cells and MV-4-11 AML cells, respectively. In 22Rv1 cells, KB-0742 rapidly downregulates nascent transcription, preferentially depleting short half-life transcripts and AR-driven oncogenic programs. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: 22Rv1 cells Concentration: 0.1 μM, 0.5 μM, 1 μM, 10 μM Incubation Time: 6 hours Result: Significant reduction of downstream phosphorylation of RNA Pol II at Ser2 and Ser7, and diminished phosphorylation at Ser5.

In Vivo

KB-0742 (3-30 mg/kg; p.o.; daily; over 21 days) is well tolerated even at high dose, while significantly reducing tumor burden in 22Rv1 human prostate cancer cell line-derived xenograft (CDX) models . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male CB17-SCID mice injected with 22Rv1 human prostate cancer cells Dosage: 3 mg/kg, 10 mg/kg, and 30 mg/kg Administration: p.o.; daily; over 21 days Result: Significantly reduced tumor growth in castration-resistant prostate cancer (CRPC).

Form:Solid

IC50& Target:CDK9/cyclinT1 6 nM (IC 50 )