Anti-angiogenic potential of small molecular inhibitors of cyclin dependent kinases in vitro.

Small molecular kinase inhibitors are promising novel drugs. Initially, they were designed for the highest possible specificity. Recently, this concept has been challenged by multikinase inhibitors, which are clinically more potent. This change of paradigm calls for re-examination of already known compounds in different functional contexts. We have compared 6 reported structurally different inhibitors of cyclin-dependent kinases (Cdks) regarding their functional effects on endothelial cells (proliferation, cell cycle, apoptosis, migration, tube formation), as well as their actions on some kinases (AKT, p38, ERK1/2, c-src, GSK3β). Only some of these compounds had anti-angiogenic effects in concentrations up to 10 μM (aminopurvalanol, indirubin-3'-monoxime, and alsterpaullone), depending on their kinase profile. Interestingly, the impact of the compounds on Cdks seemed to be of minor importance, as compared to other mechanisms. Aminopurvalanol, indirubin-3'-monoxime, and alsterpaullone might turn out as interesting scaffolds for the development of novel anti-angiogenic drugs.