POTENT INHIBITION OF CDC2 KINASE-ACTIVITY BY THE FLAVONOID L86-8275

L86-8275 [(-) ydroxy-1-methyl)-piperidinyl]-4H-benzopyran-4-one] direc tly inhibits immunoprecipitated Cdc2 kinase activity from G2/M synchro nized MDA-MB-468 breast carcinoma cells and is at least 250-fold more potent than either quercetin or genistein. Purified sea-star Cdc2 kina se (IC50 = 0.5 mu M) was inhibited with a similar potency to immunopre cipitated Cdc2 kinase from MDA-MB-468 cells (IC50 = 0.4 mu M). This in hibition was competitive with respect to ATP (K-iATP= 0.041 mu M) and noncompetitive with respect to a synthetic peptide substrate, CDK1S1 ( AAKAKKTPKKAKK-CONH2, K-iCDK1S1 = 0.14 mu M). These data suggest L86-82 75 as a lead structure for the development of inhibitors of the cyclin -dependent kinases. (C) 1994 Academic Press, Inc.