Allosteric USP7 inhibitor for neuroinflammation

A small molecule allosteric inhibitor of the deubiquitinase USP7 could help treat neuroinflammation-driven diseases. In a mouse microglial cell line, high-throughput screening identified a small-molecule derived from Eupatorium lindleyanum that decreased microglial expression of inflammatory mediators. Biochemical experiments identified USP7 as the compound's target, structural experiments showed the compound inhibited USP7 allosterically by binding its noncatalytic HUBL domain, and mass spectrometry experiments showed the compound inhibited USP7-mediated degradation of the inflammatory and redox regulator KEAP1...