BS-181 HCl

 Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Biological Activity

Description	BS-181 is a highly selective CDK7 inhibitor with IC50 of 21 nM. It is more than 40-fold selective for CDK7 than CDK1, 2, 4, 5, 6, or 9.
Targets	CDK7
IC50	21 nM [1]
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.[1]
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. [1]
Features	Demonstrates higher inhibitory selectivity for CDK7 vs. other CDKs and kinases from other classes.

Protocol(Only for Reference)

Kinase Assay: ^[1]

In vitro kinase inhibition.	Inhibition of CDK7 activity is measured by incubation of increasing amounts of BS-181 with purified recombinant CDK7/CycH/MAT1 complex, followed by measurement of free ATP remaining in the reaction using a luciferase assay, luciferase activity therefore providing a measure of inhibition of CDK7 activity for the determination of IC50.

Cell Assay: ^[1]

Cell lines	MCF-7 cells
Concentrations	Dissolved in DMSO, final concentration ~50 μM
Incubation Time	24 hours
Method	MCF-7 cells are exposed to BS-181 for 24 hours. For the determination of cell cycle and apoptosis, cells are stained with propidium iodide or labeled with Annexin V-FITC, then labeled cells are acquired within 1 hour, by using the RXP cytomics software on a Beckman Coulter Elite ESP, and the data are analyzed using Flow Jo v7.2.5. For the assessment of CDKs, cells are lysed and analyzed by western blotting.

Animal Study: ^[1]

Animal Models	MCF-7 cells are established in female nu/nu-BALB/c athymic nude mice
Dosages	10 or 20 mg/kg
Administration	Twice daily by i.p. injection
Solubility	1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL

1

References

Chemical Information

Download BS-181 HCl SDF

Chemical Name	N5-(6-aminohexyl)-N7-benzyl-3-isopropylpyrazolo[1,5-a]pyrimidine-5,7-diamine hydrochloride

Preparing Stock Solutions

Stock Solution (1ml DMSO)	1mM	10mM	20mM	30mM
Mass(mg)	0.41699	4.1699	8.3398	12.5097

Customer Reviews (1)

Click to enlarge	Rating
	Source	Dr. Vladimir Krystof of Palacky University. BS-181 HCl purchased from Selleck
	Method	Western blot
	Cell Lines	MCF-7 cells
	Concentrations	0.0001-10 μM
	Incubation Time	24 h
	Results	Dose-response inhibition of purified human recombinant cyclin-dependent kinase CDK7/cyclin H by inhibitor BS-181 (left panel).

Product Citations (1)

• 
  

  Cyclin-Dependent Kinase 9 inhibition protects cartilage from the catabolic effects of pro-inflammatory cytokines. [Yik JH, et al. Arthritis Rheumatol 2014;10.1002/art.38378]