Small molecule inhibitors of cyclin-dependent kinases (CDK) have been developed as anticancer drugs with cytostatic and cytotoxic properties, but some of them have also been shown to limit angiogenesis. Here, we report that the 3,5-diaminopyrazole CAN508 inhibits endothelial cell migration and tube formation. In addition, it reduces phosphorylation of the C-terminus of RNA polymerase II and inhibits mRNA synthesis in endothelial cells, in accordance with previous observations that it has high selectivity towards the positive transcriptional regulator P-TEFb. Moreover, CAN508 reduces expression of vascular endothelial growth factor by several human cancer cell lines. The findings suggest that P-TEFb may be an attractive target for anti-angiogenic therapy.
- MeSH
- azosloučeniny farmakologie MeSH
- fosforylace MeSH
- genetická transkripce účinky léků MeSH
- inhibitory proteinkinas farmakologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- patologická angiogeneze prevence a kontrola MeSH
- pyrazoly farmakologie MeSH
- RNA-polymerasa II metabolismus MeSH
- transkripční faktor B aktivující elongaci antagonisté a inhibitory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
