Nature Communications (Feb 2023)

Accelerating inhibitor discovery for deubiquitinating enzymes

  • Wai Cheung Chan,
  • Xiaoxi Liu,
  • Robert S. Magin,
  • Nicholas M. Girardi,
  • Scott B. Ficarro,
  • Wanyi Hu,
  • Maria I. Tarazona Guzman,
  • Cara A. Starnbach,
  • Alejandra Felix,
  • Guillaume Adelmant,
  • Anthony C. Varca,
  • Bin Hu,
  • Ariana S. Bratt,
  • Ethan DaSilva,
  • Nathan J. Schauer,
  • Isabella Jaen Maisonet,
  • Emma K. Dolen,
  • Anthony X. Ayala,
  • Jarrod A. Marto,
  • Sara J. Buhrlage

DOI
https://doi.org/10.1038/s41467-023-36246-0
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 13

Abstract

Read online

Deubiquitinases (DUBs) are key signaling enzymes, many of which lack selective inhibitors. Chan et al. pair a DUB-focused covalent library to mass spectrometry activity-based protein profiling, leading to selective hits against 23 endogenous DUBs and a first-in-class VCPIP1 probe with nanomolar potency.