| Chemical Properties | Back Directory | [storage temp. ]
4°C, away from moisture | [solubility ]
|DMSO : 62.5 mg/mL (173.45 mM; Need ultrasonic) | [form ]
Solid | [color ]
Light yellow to yellow | [Water Solubility ]
Water : 100 mg/mL (277.52 mM; Need ultrasonic) |
| Hazard Information | Back Directory | [Uses]
KB-0742 dihydrochloride is a potent, selective and orally active CDK9 inhibitor with an IC50 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[1]. | [Biological Activity]
KB-0742 dihydrochloride is a potent, selective and orally active CDK9 inhibitor with an IC50 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[1].
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)[1].KB-0742 (48-72 hours) treatment shows cytostatic effects in prostate cancer and leukemia cell lines. KB-0742 shows antiproliferative activity with GR50s of 0.183 μM and 0.288 μM for 22Rv1 cells and MV-4-11 AML cells, respectively[1].In 22Rv1 cells, KB-0742 rapidly downregulates nascent transcription, preferentially depleting short half-life transcripts and AR-driven oncogenic programs[1].
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[1]. | [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[1]. | Animal Model: | Male CB17-SCID mice injected with 22Rv1 human prostate cancer cells[1] | | 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). |
| [IC 50]
CDK9/cyclinT1: 6 nM (IC50) | [storage]
4°C, away from moisture | [References]
[1]. André Richters, et al. Modulating Androgen Receptor-Driven Transcription in Prostate Cancer with Selective CDK9 Inhibitors. Cell Chem Biol. 2020 Oct 20;S2451-9456(20)30380-9. |
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