title: The selective P-TEFb inhibitor CAN508 targets angiogenesis.
abstract: 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.
authors.affiliation: Laboratory of Growth Regulators, Faculty of Science, Palacký University & Institute of Experimental Botany ASCR, Šlechtitelů 11, 783 71 Olomouc, Czech Republic. vladimir.krystof@upol.cz
authors.forename: Vladimír
authors.initials: V
authors.lastname: Kryštof
authors.forename: Lucie
authors.initials: L
authors.lastname: Rárová
authors.forename: Johanna
authors.initials: J
authors.lastname: Liebl
authors.forename: Stefan
authors.initials: S
authors.lastname: Zahler
authors.forename: Radek
authors.initials: R
authors.lastname: Jorda
authors.forename: Jiří
authors.initials: J
authors.lastname: Voller
authors.forename: Petr
authors.initials: P
authors.lastname: Cankař
mesh_terms: D001391:Azo Compounds / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010766:Phosphorylation; D042925:Positive Transcriptional Elongation Factor B / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D001391:Azo Compounds; C568946:CAN 508; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D012333:RNA, Messenger; D042925:Positive Transcriptional Elongation Factor B; D012319:RNA Polymerase II