CDK7 inhibitor BS-181 Small Molecule (Tool Compound)
- Name R Charles Coombes
- Institute Imperial College
Tool name: CDK7 inhibitor BS-181 Small Molecule (Tool Compound)
Molecular formula: C22H32N6.HCl
Tool type: Small molecules
Tool sub-type: Inhibitor
Description: BS-181 is a highly selective CDK inhibitor for CDK7 (and with lower selectivity to other kinases) with antitumoral activity in vitro and no apparent toxicity.
Cyclin-dependent protein kinases (CDKs) have a central function in the regulation of cell proliferation, apoptosis and gene expression. CDK7 regulates the activation of CDK1, CDK2, CDK4, CDK5 and CDK6 and is involved in the regulation of transcription as part of the transcription factor TFIIHcomplex. A common feature of cancer is the over-expression of CDK7, making it an attractive target for anti-cancer drug development. The pyrazolo[1,5-a] pyrimidine compound BS-181 is a highly selective CDK7 inhibitor (IC50: 21 nM) with 42-fold selectivity over CDK2 (IC50: 880 nM), which is the only other CDK that is inhibited in concentrations lower than 1 M. In MCF-7 cells, BS-181 inhibited the phosphorylation of CDK7 substrates, promoted cell cycle arrest and apoptosis to inhibit the growth of cancer cell lines, and showed antitumor effects in vivo. The compound was stable in vivo with a plasma elimination half-life in mice of 405 minutes after i.p. administration of 10 mg/kg. The same dose of compound inhibited the growth of MCF-7 human xenografts in nude mice.
Research area: Cancer
- For Research Use Only
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