2. Academic Validation
  3. Studies on cyclin-dependent kinase inhibitors: indolo-[2,3-a]pyrrolo[3,4-c]carbazoles versus bis-indolylmaleimides

Studies on cyclin-dependent kinase inhibitors: indolo-[2,3-a]pyrrolo[3,4-c]carbazoles versus bis-indolylmaleimides

  • Bioorg Med Chem Lett. 2003 Nov 3;13(21):3841-6. doi: 10.1016/s0960-894x(03)00792-3.
Concha Sanchez-Martinez 1,  Chuan Shih,  Guoxin Zhu,  Tiechao Li,  Harold B Brooks,  Bharvin K R Patel,  Richard M Schultz,  Tammy B DeHahn,  Charles D Spencer,  Scott A Watkins,  Catherine A Ogg,  Eileen Considine,  Jack A Dempsey,  Faming Zhang
Affiliations

Affiliation

  • 1 DCR&T, Lilly Spain S.A., Avda de la Industria 30, 28108 Alcobendas, Madrid, Spain. [email protected]
PMID: 14552792 DOI: 10.1016/s0960-894x(03)00792-3
Abstract

A series of indolo[2,3-a]pyrrolo[3,4-c]carbazoles and their bis-indolylmaleimides precursors have been prepared in order to compare their activity as D1-CDK4 inhibitors. Both enzymatic and antiproliferative assays have shown that the structurally more constrained indolo[2,3-a]pyrrolo[3,4-c]carbazoles are consistently more active (8-42-fold) in head-to-head comparison with their bis-indolylmaleimides counterparts. Cell-cycle analysis using flow cytometry have also shown that the indolocarbazoles are selective G1 blockers while the bis-indolylmaleimides arrest cells in the G2/M phase.

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