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Updated: May 27, 2026

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors
Published on: August 17, 2019
Novel ATP competitive MK2 inhibitors with potent biochemical and cell-based activity throughout the series
Arthur Oubrie1, Allard Kaptein, Edwin de Zwart
1Merck Research Laboratories, MSD, PO Box 20, 5340 BH Oss, The Netherlands.
Abstract:
Optimization of our previously described pyrrolopiperidone series led to the identification of a new benzamide sub-series, which exhibits consistently high potency in biochemical and cell-based assays throughout the series. Strong inhibition of LPS-induced production of the cytokine TNFα is coupled to the regulation of HSP27 phosphorylation, indicating that the observed cellular effects result from the inhibition of MK2. X-ray crystallographic and computational analyses provide a rationale for the high potency of the series.
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