Purvalanol A

Purvalanol A is a potent CDK 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, resepctively. IC50 & Target: IC50: 4 nM (cdc2-cyclin B), 70 nM (cdk2-cyclin A), 35 nM (cdk2-cyclin E), 850 nM (cdk4-cyclin D1), 75 nM (cdk5-p35)^[1] In Vitro: Purvalanol A inhibits cdc28 (S. cerevisiae) and erk1 with IC₅₀s of 80 and 9000 nM. Purvalanol A shows inhibitory activities against the NCI panel of 60 human tumor cell lines, with average GI50 of 2 μM; two cell lines show an -20-fold increase in sensitivity to purvalanol A: the KM12 colon cancer cell line with a GI₅₀ of 76 nM and the NCI-H522 non–small cell lung cancer cell line with a GI₅₀ of 347 nM^[1]. Purvalanol A is a 2.5-fold more potent inhibitor of CDK2, but also inhibits DYRK1A potently and a number of other protein kinases in the low micromolar range. Purvalanol A inhibits MKK1, MAPK2/ERK2, JNK/SAPK1c with IC₅₀s of 80, 26, 84 μM^[2]. Purvalanol A selectively inhibits the phosphorylation of cellular proteins. Purvalanol A prevents the increases of the contents of cyclins D and E during serum-induced G1 phase progression. Purvalanol A does not inhibit transcription under cell-free conditions^[3].