Butyrolactone I

Butyrolactone I is a selective small molecule inhibitor of cyclin-dependent kinase (CDK) enzymes, specifically inhibiting Cdk2 and Cdc2 kinase. The inhibitory effect Butyrolactone I is due to competition with ATP binding at CDK. Activating phosphorylation of the transcription factor E2F-1 is blocked by Butyrolactone I. The cdc2-like kinase responsible for phosphorylation of tau protein is shown to be inhibited by Butyrolactone I - the phosphorylation and electrophoretic mobility shift of microtuble tau components in cerebral cells incubated with ATP were both suppressed by Butyrolactone I. In PANC-1 and AsPC-1 cells, Butyrolactone I demonstrates significant suppression of pRb phosphorylation and Cyclin A expression, upregulation of Bax expression, and downregulation of Bcl-2 expression. Butyrolactone I is an inhibitor of Cdk1, Cdk5 and cyclin B.