Uses
BS-181 is a potent and selective CDK7 inhibitor (IC50=21 nM) than Seliciclib (HY-30237). BS-181 is also against CDK2, CDK5 and CDK9 with IC50 values of 880, 3000 and 4200 nM, respectively (fails to block CDK1, 4 and 6). BS-181 inhibits a panel of cancer cells growth (IC50=11.5 μM-37.3 μM) and induces cell apoptosis. BS-181 has the potential for the research of cancer therapy[1][2].
Definition
ChEBI: N5-(6-aminohexyl)-N7-(phenylmethyl)-3-propan-2-ylpyrazolo[1,5-a]pyrimidine-5,7-diamine is a pyrazolopyrimidine.
in vivo
BS-181 (intraperitoneal injection; 5 mg/kg or 10 mg/kg twice daily; total daily doses of 10 mg/kg or 20 mg/kg; 14 days) inhibitstumor growth in a dose-dependent manner.Tumor growth exhibits 25% and 50% reduction compared with the control group, for 10 mg/kg/day and 20 mg/kg/day, respectively[1].
| Animal Model: | 7-week old female nu/nu-BALB/c athymic nude micewith MCF-7 cells[1] |
| Dosage: | 5 mg/kg or 10 mg/kg; 10 mg/kg or 20 mg/kg |
| Administration: | Intraperitoneal injection; twice daily or once total daily; 14 days |
| Result: | Inhibited tumor growth significantly. |
IC 50
CDK7/CycH/MAT1: 0.021 μM (IC
50); CDK2/Cyc E: 0.88 μM (IC
50); CDK5/p35NCK: 3 μM (IC
50); CDK9/cycT: 4.2 μM (IC
50); CDK1/cycB: 8.1 μM (IC
50); CDK4/Cyc D1: 33 μM (IC
50); CDK6/cycD1: 47 μM (IC
50)
References
[1] Ali S et al. The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity. Cancer Res. 2009 Aug 1;69(15):6208-15. DOI:
10.1158/0008-5472.CAN-09-0301[2] Wang BY, et al. Selective CDK7 inhibition with BS-181 suppresses cell proliferation and induces cell cycle arrest and apoptosis in gastric cancer. Drug Des Devel Ther. 2016 Mar 16;10:1181-9. DOI:
10.2147/DDDT.S86317
