Modulating the interaction between CDK2 and cyclin A with a quinoline-based inhibitor
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- 作者：Yongqi Deng ; Gerald W. Shipps Jr. ; Lianyun Zhao ; M. Arshad Siddiqui ; Janeta Popovici-Muller ; Patrick J. Curran ; Jose S. Duca ; Alan W. Hruza ; Thierry O. Fischmann ; Vincent S. Madison ; Rumin Zhang ; Charles W. McNemar ; Todd W. Mayhood ; Rosalinda Syto ; Allen Annis ; Paul Kirschmeier ; Emma M. Lees ; David A. Parry ; William T. Windsor
- 关键词：Kinases ; Tumor ; CDK2 ; Modulator ; High throughput screening
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：1 January, 2014
- 年：2014
- 卷：24
- 期：1
- 页码：199-203
- 全文大小：1107 K
文摘
A new class of quinoline-based kinase inhibitors has been discovered that both disrupt cyclin dependent 2 (CDK2) interaction with its cyclin A subunit and act as ATP competitive inhibitors. The key strategy for discovering this class of protein-protein disrupter compounds was to screen the monomer CDK2 in an affinity-selection/mass spectrometry-based technique and to perform secondary assays that identified compounds that bound only to the inactive CDK2 monomer and not the active CDK2/cyclin A heterodimer. Through a series of chemical modifications the affinity (Kd) of the original hit improved from 1 to 0.005 渭M.