BibTex format
@article{Panyain:2020:10.1021/jacs.0c04527,
author = {Panyain, N and Godinat, A and Lanyon-Hogg, T and Lachiondo-Ortega, S and Will, EJ and Soudy, C and Mondal, M and Mason, K and Elkhalifa, S and Smith, L and Harrigan, JA and Tate, EW},
doi = {10.1021/jacs.0c04527},
journal = {Journal of the American Chemical Society},
pages = {12020--12026},
title = {Discovery of a potent and selective covalent inhibitor and activity-based probe for the deubiquitylating enzyme UCHL1, with anti-fibrotic activity},
url = {http://dx.doi.org/10.1021/jacs.0c04527},
volume = {142},
year = {2020}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a deubiquitylating enzyme which is proposed as a potential therapeutic target in neurodegeneration, cancer, and liver and lung fibrosis. Herein we report the discovery of the most potent and selective UCHL1 probe (IMP-1710) to date based on a covalent inhibitor scaffold and apply this probe to identify and quantify target proteins in intact human cells. IMP-1710 stereoselectively labels the catalytic cysteine of UCHL1 at low nanomolar concentration in cells. We further demonstrate that potent and selective UCHL1 inhibitors block pro-fibrotic responses in a cellular model of idiopathic pulmonary fibrosis, supporting the potential of UCHL1 as a potential therapeutic target in fibrotic diseases.
AU - Panyain,N
AU - Godinat,A
AU - Lanyon-Hogg,T
AU - Lachiondo-Ortega,S
AU - Will,EJ
AU - Soudy,C
AU - Mondal,M
AU - Mason,K
AU - Elkhalifa,S
AU - Smith,L
AU - Harrigan,JA
AU - Tate,EW
DO - 10.1021/jacs.0c04527
EP - 12026
PY - 2020///
SN - 0002-7863
SP - 12020
TI - Discovery of a potent and selective covalent inhibitor and activity-based probe for the deubiquitylating enzyme UCHL1, with anti-fibrotic activity
T2 - Journal of the American Chemical Society
UR - http://dx.doi.org/10.1021/jacs.0c04527
UR - https://pubs.acs.org/doi/10.1021/jacs.0c04527
UR - http://hdl.handle.net/10044/1/80205
VL - 142
ER -
