CDK2 is a serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. CDK2 triggers duplication of centrosomes and DNA, acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression. CDK2 controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Purvalanol A is a CDK2 inhibitor, which inhibits cdc2-cyclin B, cdk2-cyclin A, cdk2-cyclin E, cdk4-cyclin D1, and cdk5-p35 with IC50s of 4, 70, 35, 850, 75 nM, respectively. Based on kinase assays performed in immunoprecipitates, the IC50s of purvalanol A against 2 yeast CDKs (Cdc28p and Pho85p) were 7 μM and 2 μM, respectively[3]. According to a MTT cell viability assay, purvalanol A induced cell viability loss by 50% in MCF-7 cells at the concentration of 25 μM when incubated in vitro for 24h[4].In a spinal cord injury model established in Sprague–Dawley rats, 5 μl of purvalanol A at the concentration of 10 mM in DMSO was immediately injected into the injury site. The results were that purvalanol A restricted compaction of the injury cavity and astrocyte infiltration into the cavity. Purvalanol A treatment also attenuated regenerative responses of anterogradely labeled corticospinal tract axons. Moreover, purvalanol A treatments reduced astrocyte migration and in parallel retarded the extension of spinal axon, observed by the technique of implantation of a polymeric tube into the spinal cord[5].
作用机制
Purvalanol A is a CDK2 inhibitor that acts by blocking the ATP-binding site[3].
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