2. Academic Validation
  3. Synthesis, structure-activity relationship, and biological studies of indolocarbazoles as potent cyclin D1-CDK4 inhibitors

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

  • J Med Chem. 2003 May 22;46(11):2027-30. doi: 10.1021/jm0256169.
Guoxin Zhu 1,  Scott E Conner,  Xun Zhou,  Chuan Shih,  Tiechao Li,  Bryan D Anderson,  Harold B Brooks,  Robert Morris Campbell,  Eileen Considine,  Jack A Dempsey,  Margaret M Faul,  Cathy Ogg,  Bharvin Patel,  Richard M Schultz,  Charles D Spencer,  Beverly Teicher,  Scott A Watkins
Affiliations

Affiliation

  • 1 Lilly Research Laboratories, A Division of Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. [email protected]
PMID: 12747775 DOI: 10.1021/jm0256169
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.

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