KB-0742 dihydrochloride manufacturers
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| | KB-0742 dihydrochloride Basic information |
| Product Name: | KB-0742 dihydrochloride | | Synonyms: | KB-0742 dihydrochloride;KB0742,inhibit,CDK,CDK9,KB-0742,KB 0742,Ser7,Ser2,CRPC,KB 0742 dihydrochloride,antiproliferative,Cyclin dependent kinase,Ser5,oral,Inhibitor,KB0742 dihydrochloride,anticancer;(1S,3S)-N1-(5-(Pentan-3-yl)pyrazolo[1,5-a]pyrimidin-7-yl)cyclopentane-1,3-diamine dihydrochloride;KB-0742 dihydrochloride, 10 mM in DMSO;KB-0742 Dihydrochloride ，S9901;KB-0742 2HCl | | CAS: | 2416874-75-2 | | MF: | C16H26ClN5 | | MW: | 323.87 | | EINECS: | | | Product Categories: | | | Mol File: | 2416874-75-2.mol |  |
| | KB-0742 dihydrochloride Chemical Properties |
| 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) |
| | KB-0742 dihydrochloride Usage And Synthesis |
| 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) | | 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. |
| | KB-0742 dihydrochloride Preparation Products And Raw materials |
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