BS-181

Cas No.:	1092443-52-1
Chemical Name:	BS-181
Synonyms:	BS-181 hydrochloride;BS-181;5-N-(6-aminohexyl)-7-N-benzyl-3-propan-2-ylpyrazolo[1,5-a]pyrimidine-5,7-diamine,hydrochloride;BS181;N5-(6-aminohexyl)-N7-benzyl-3-isopropylpyrazolo[1,5-a]pyrimidine-5,7-diamine;BCP9000454;BCPP000314;BS-181 HCl;cc-578;N5-(6-aminohexyl)-N7-benzyl-3-iso-propylpyrazolo[1,5-a]pyrimidine-5,7-diamine;S1572_Selleck;N5-(6-Aminohexyl)-3-isopropyl-N7-benzylpyrazolo[1,5-a]pyrimidine-5,7-diamine
SMILES:	CC(C1=C(N=C(C=C2NCC3=CC=CC=C3)NCCCCCCN)N2N=C1)C
Formula:	C22H32N6.HCl
M.Wt:	416.99062
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	BS-181 is a highly selective CDK7 inhibitor with IC50 of 21 nM. ; >40-fold selective for CDK7 than CDK1, 2, 4, 5, 6, or 9. IC50 Value: 21 nM in vitro: BS-181 is a small molecule inhibitor of CDK7 in a cell-free environment, which displays more potential activity than roscovitine with IC 50 of 510 nM. Among the CDKs and other 69 kinases from many different classes, BS-181 shows high inhibitory selectivity for CDK7, inhibits CDK2 at concentrations lower than 1 μM which being inhibited 35-fold less potently (IC50 with 880 nM) than CDK7, shows slight inhibition for CDK1, CDK4, CDK5, CDK6 and CDK9 with IC50 values higher than 3.0 μM, and only shows inhibition for several kinases from other classes at high concentrations (>10 μM). BS-181 promotes cell cycle arrest and inhibits the cancer cell growth of a range of tumor types, including breast, lung, prostate and colorectal cancer with IC50 in the range of 11.5-37 μM. In MCF-7 cells, BS-181 inhibits the phosphorylation of the CDK7 substrate RNA polymerase II COOH-terminal domain (CTD), and promotes cell cycle arrest and apoptosis to inhibit the growth of cancer cell lines. in vivo: BS-181 is stable in vivo with a plasma elimination half-life in mice of 405 minutes after i.p. administration of 10 mg/kg. BS-181 inhibits the growth of MCF-7 xenografts in the nude mice model in a dose-dependent manner, with 25% and 50% reduction in tumor growth after 2 weeks of treatment at 10 mg/kg/day and 20 mg/kg/day, respectively without apparent toxicity. For the detailed information of BS-181 hydrochloride, the solubility of BS-181 hydrochloride in water, the solubility of BS-181 hydrochloride in DMSO, the solubility of BS-181 hydrochloride in PBS buffer, the animal experiment (test) of BS-181 hydrochloride, the cell expriment (test) of BS-181 hydrochloride, the in vivo, in vitro and clinical trial test of BS-181 hydrochloride, the EC50, IC50,and affinity,of BS-181 hydrochloride, For the detailed information of BS-181 hydrochloride, the solubility of BS-181 hydrochloride in water, the solubility of BS-181 hydrochloride in DMSO, the solubility of BS-181 hydrochloride in PBS buffer, the animal experiment (test) of BS-181 hydrochloride, the cell expriment (test) of BS-181 hydrochloride, the in vivo, in vitro and clinical trial test of BS-181 hydrochloride, the EC50, IC50,and affinity,of BS-181 hydrochloride, Please contact DC Chemicals.
In Vivo:	BS-181 (5 mg/kg, 10 mg/kg, i.p.) inhibits the growth of MCF-7 tumors in nude mice. Intravenous (i.v) and i.p administration of 10 mg/kg BS-181 shows rapid clearance[1]. BS-181 (10 mg/kg/d or 20 mg/kg/d, i.p.) significantly inhibits the growth of tumor in a dose-dependent manner compared to the control group[2].
In Vitro:	BS-181 promotes cell cycle arrest and inhibits cancer cell growth, and growth is inhibited for all cell lines tested, with IC50 values ranging from 11.5 to 37 μM. BS-181 inhibits RB phosphorylation at Ser795 and Ser821 with an apparent IC50 of 15 μM, similar to the IC50 obtained for P-Ser2 inhibition. BS-181 treatment of MCF-7 cells leads to G1 arrest at and apoptosis[1]. BS-181 inhibits GC cell and normal gastric epithelial RGM-1 cell line growth with inhibitory concentration (IC50) ranging from 17 to 22 μM and 6.5 μM, respectively. BS-181 significantly inhibits cell migration and invasion ability in a dose-dependent manner[2].
Cell Assay:	Cell viability is detected using Cell Counting Kit (CCK-8 kit) according to supplier’s introductions. Briefly, BGC823 cells are seeded at 104 cells per well for 48 hours with or without BS-181. Then, the absorbance is detected at 450 nm (reference at 650 nm) in each well.
Animal Administration:	In total, 5×106 BGC823 cells (0.1 mL) are injected subcutaneously into the flank of the mice. Tumor measurements are performed two times per week, and volumes are calculated using the formula: tumor size=(length [mm] × width2 [mm])/2. Finally, 30 mice (tumor volume 100-200 mm3) are selected and randomLy assigned into three groups. As previously described, BS-181 is prepared in 10% dimethyl sulfoxide/50 mM HCl/5% Tween 20/85% saline. Micereceive BS-181 injection (ip) twice daily at indicated doses (BS-181 [10 mg/kg/d or 20 mg/kg/d] or roscovitine [20 mg/kg/d]) for a total of 14 days. Control mice are injected with vehicles. Animal weights and tumor volume are measured each day throughout the 14-day treatment. In addition, all rats are kept for another 30 days for survival observation. Mice are injected intraperitoneally twice daily with BS-181 at 5 mg/kg or 10 mg/kg.
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. [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.