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Discovery of a Novel Series of CHK1 Kinase Inhibitors with a Distinctive Hinge Binding Mode.

ABSTRACT: A novel series of CHK1 inhibitors with a distinctive hinge binding mode, exemplified by 2-aryl-N-(2-(piperazin-1-yl)phenyl)thiazole-4-carboxamide, was discovered through high-throughput screening using the affinity selection-mass spectrometry (AS-MS)-based Automated Ligand Identification System (ALIS) platform. Structure-based ligand design and optimization led to significant improvements in potency to the single digit nanomolar range and hundred-fold selectivity against CDK2.

SUBMITTER: Huang X

PROVIDER: S-EPMC4025668 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Discovery of a Novel Series of CHK1 Kinase Inhibitors with a Distinctive Hinge Binding Mode.

Huang Xiaohua X Cheng Cliff C CC Fischmann Thierry O TO Duca José S JS Yang Xianshu X Richards Matthew M Shipps Gerald W GW

ACS medicinal chemistry letters 20120120 2

A novel series of CHK1 inhibitors with a distinctive hinge binding mode, exemplified by 2-aryl-N-(2-(piperazin-1-yl)phenyl)thiazole-4-carboxamide, was discovered through high-throughput screening using the affinity selection-mass spectrometry (AS-MS)-based Automated Ligand Identification System (ALIS) platform. Structure-based ligand design and optimization led to significant improvements in potency to the single digit nanomolar range and hundred-fold selectivity against CDK2. ...[more]

PMID: 24900442

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