BS-181

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

BS-181 是一种有效的选择性 CDK7 抑制剂，IC50 为 21 nM。

BS-181 is a potent, selective CDK7 inhibitor with IC50 of 21 nM, 40-fold selectivity over CDK2/cycE and no significant activity against CDK1/cycB, CDK4/cycD1, CDK5/p35NCK, CDK6/cycD1, and CDK9/cycT (IC50>1 uM); promotes cell cycle arrest and inhibits cancer cell growth in a panel of cell lines representing a range of tumor types (IC50=1.5 to 37 uM), inhibits the phosphorylation of CDK7 substrates, inhibits phosphorylation of the RNA polymerase II COOH-terminal domain (CTD) at P-Ser5 (IC50=9 uM), inhibits RB phosphorylation at Ser795 and Ser821 (IC50=15 uM); induces apoptosis in vitro, and shows antitumor effects in vivo.

BS-181 (0-40 μM; 72 hours) inhibits cancer cells growth, it is against Breast cancer cell lines growth with IC50 values ranging from 15.1 μM to 20 μM, it is against Colorectal cancer cell lines growth with IC50 values ranging from 11.5 μM to15.3 μM and is against lung, osteosarcoma, prostate and liver cancer cell lines with IC50 values ranging from 11.5 μM to 37.3 μM, respectively.BS-181 (0-50 μM; 4 hours) shows inhibition of phosphorylation of the RNA polymerase II C-terminal domain (CTD) at serine 5 (P-Ser5). It down-regulates CDK4 and cyclin D1 expression while does not effect other CDKs and cyclins.BS-181 (0-50 μM; 24 hours) shows an increase in cells in G1, accompanied by a reduction in cell numbers in S and G2/M at low concentrations. At higher concentrations, however, cells accumulates in the sub-G1, indicative of apoptosis. Cell Proliferation Assay Cell Line:Breast cancer cell line: MCF-7, MDA-MB-231, T47D, ZR-75-1, etcColorectal cancer cell line: COLO-205, HCT-116, HCT-116 (p53-/-)Lung cancer cell line: A549, NCI-460 Osteosarcoma cancer cell line: U2OS, SaOS2 Prostate cancer cell line: PC3, LNCaP Concentration:0-50 μM Incubation Time:4 hours Result:Had anti-proliferative activities against a panel of cell lines, including breast, lung, prostate and colorectal cancer.Western Blot Analysis Cell Line:MCF-7 cells Concentration:0-40 μM Incubation Time:72 hours Result:Inhibited phosphorylation of CDK7 substrates.Apoptosis Analysis Cell Line:MCF-7 cells Concentration:0-50 μM Incubation Time:24 hours Result:Led cells to G1 arrest and apoptosis.

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. Animal Model:7-week old female nu/nu-BALB/c athymic nude mice?with MCF-7 cells 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.

BS 181 | BS181

Angiogenesis

CDK

CDK7

Cancer

——

1092443-52-1

380.53

C22H32N6

>98% (HPLC)

10 mM in DMSO

CC(C)C1=C2N=C(NCCCCCCN)C=C(NCC3=CC=CC=C3)N2N=C1

Pyrazolo[1,5-a]pyrimidine-5,7-diamine, N5-(6-aminohexyl)-3-(1-methylethyl)-N7-(phenylmethyl)-

(-20℃)

With Ice Pack

≥ 2 years