Wednesday, December 14, 2016

Metabolically Labile Fumarate Esters Impart Kinetic Selectivity to Irreversible Inhibitors

Metabolically Labile Fumarate Esters Impart Kinetic Selectivity to Irreversible Inhibitors

Balyn W. Zaro, Landon R. Whitby, Kenneth M. Lum, and Benjamin F. Cravatt*
The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
J. Am. Chem. Soc.2016138 (49), pp 15841–15844

The use of a fumarate ester warhead is found to confer greater selectivity than a simple acrylamide warhead for inhibition of Bruton's Tyrosine Kinase (BTK).

A covalent irreversible inhibitor binds in two mutually exclusive conformations to the active-site cysteine residue of human aldehyde dehydrogenase 1A3

Daniela Covaleda, David Vizarraga, Tulsi Upadhyay, Jiyun Zhu, Daniel Abegg, Raquel Pequerul, Martín Hugo, Alexander Adibekian, Ignacio Fita,...