Document Report Card

ID: ALA1145043

Journal: J Med Chem

Title: Synthesis, structure-activity relationship, and biological studies of indolocarbazoles as potent cyclin D1-CDK4 inhibitors.

Authors: Zhu G, Conner SE, Zhou X, Shih C, Li T, Anderson BD, Brooks HB, Campbell RM, Considine E, Dempsey JA, Faul MM, Ogg C, Patel B, Schultz RM, Spencer CD, Teicher B, Watkins SA.

Abstract: Novel substituted indolocarbazoles were synthesized, and their kinase inhibitory capability was evaluated in vitro. 6-Substituted indolocarbazoles 4 were found to be potent and selective D1/CDK4 inhibitors. 4d and 4h exhibited potent and ATP-competitive D1/CDK4 activities with IC50 values of 76 and 42 nM, respectively. Both compounds had high selectivity against the other kinases. These D1/CDK4 inhibitors inhibited tumor cell growth, arrested tumor cells at the G1 phase, and inhibited pRb phosphorylation.

CiteXplore: 12747775

DOI: 10.1021/jm0256169