The selective P-TEFb inhibitor CAN508 targets angiogenesis

被引：31

作者：

Krystof, Vladimir ^{[1
,2
]}

Rarova, Lucie ^{[3
]}

Liebl, Johanna ^{[4
]}

Zahler, Stefan ^{[4
]}

Jorda, Radek ^{[1
,2
]}

Voller, Jiri ^{[3
]}

Cankar, Petr ^{[5
]}

机构：

[1] Palacky Univ, Fac Sci, Lab Growth Regulators, Slechtitelu 11, Olomouc 78371, Czech Republic

[2] Inst Expt Bot ASCR, Olomouc 78371, Czech Republic

[3] Palacky Univ, Dept Growth Regulators, Fac Sci, Ctr Reg Hana Biotechnol & Agr Res, Olomouc 78371, Czech Republic

[4] Univ Munich, Ctr Drug Res, Dept Pharm, D-81377 Munich, Germany

[5] Palacky Univ, Fac Sci, Dept Organ Chem, Olomouc 77146, Czech Republic

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 09期

关键词：

Angiogenesis; Cancer; Transcription; Inhibitor; Cyclin-dependent kinase 9; P-TEFb; GROWTH-FACTOR EXPRESSION; I-KAPPA-B; KINASE INHIBITOR; CYCLIN D1; CELL MIGRATION; P53; FLAVOPIRIDOL; APOPTOSIS; CANCER; PHOSPHORYLATION;

D O I：

10.1016/j.ejmech.2011.06.035

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：4289 / 4294

页数：6

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