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High-Throughput Discovery and Characterization of Covalent Inhibitors for Protein Tyrosine Phosphatases

  • Zihan Qu,
  • Aaron D. Krabill,
  • Zhong-Yin Zhang

摘要

Covalent inhibition has gained increasing interest in targeting the undruggable protein tyrosine phosphatases (PTPs). However, a systematic method for discovering and characterizing covalent PTP inhibitors has yet to be established. Here, we describe a workflow involving high-throughput screening of covalent fragment libraries and a novel biochemical assay that enables the acquisition of kinetics parameters of PTP inhibition by covalent inhibitors with higher throughput.