Fragment Screening Identifies Novel Allosteric Binders and Binding Sites in the VHR (<i>DUSP3</i>) Phosphatase.

ABSTRACT: The human Vaccinia H1-related phosphatase (VHR; DUSP3) is a critical positive regulator of the innate immune response. Recent studies suggest that inhibiting VHR could be beneficial in treating sepsis and septic shock. VHR belongs to the superfamily of protein tyrosine phosphatases (PTPs), a large class of enzymes that are notoriously difficult to target with small molecules. Fragment-based drug discovery (FBDD) has emerged as an effective strategy for generating potent ligands, even for challenging drug targets. Here, we present a fluorine NMR-based discovery platform for identifying fragments that bind to VHR. This platform encompasses automated library assembly, mixture formation, quantitative material transfer, fluorine NMR screening, and biophysical hit confirmation. We

SUBMITTER: Wu J 

PROVIDER: S-EPMC11822521 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature