新型、强效且选择性的细胞周期蛋白D1/细胞周期蛋白依赖性激酶4抑制剂：吲哚并[6,7-a]吡咯并[3,4-c]咔唑

Novel, potent and selective cyclin D1/CDK4 inhibitors: indolo[6,7-a]pyrrolo[3,4-c]carbazoles.

作者信息

Engler Thomas A, Furness Kelly, Malhotra Sushant, Sanchez-Martinez Concha, Shih Chuan, Xie Walter, Zhu Guoxin, Zhou Xun, Conner Scott, Faul Margaret M, Sullivan Kevin A, Kolis Stanley P, Brooks Harold B, Patel Bharvin, Schultz Richard M, DeHahn Tammy B, Kirmani Kashif, Spencer Charles D, Watkins Scott A, Considine Eileen L, Dempsey Jack A, Ogg Catherine A, Stamm Nancy B, Anderson Bryan D, Campbell Robert M, Vasudevan Vasu, Lytle Michelle L

机构信息

Lilly Research Laboratories, Eli Lilly and Company, 46285, Indianapolis, IN, USA.

出版信息

Bioorg Med Chem Lett. 2003 Jul 21;13(14):2261-7. doi: 10.1016/s0960-894x(03)00461-x.

DOI:10.1016/s0960-894x(03)00461-x

PMID:12824014

Abstract

The synthesis and CDK inhibitory properties of a series of indolo[6,7-a]pyrrolo[3,4-c]carbazoles is reported. In addition to their potent CDK activity, the compounds display antiproliferative activity against two human cancer cell lines. These inhibitors also effect strong G1 arrest in these cell lines and inhibit Rb phosphorylation at Ser780 consistent with inhibition of cyclin D1/CDK4.

摘要

报道了一系列吲哚并[6,7-a]吡咯并[3,4-c]咔唑的合成及其对细胞周期蛋白依赖性激酶（CDK）的抑制特性。除了具有强大的CDK活性外，这些化合物还对两种人类癌细胞系显示出抗增殖活性。这些抑制剂还能使这些细胞系发生强烈的G1期阻滞，并抑制Ser780位点的视网膜母细胞瘤蛋白（Rb）磷酸化，这与细胞周期蛋白D1/CDK4的抑制作用一致。