Structural Basis for Isoform Selective Nitric Oxide Synthase Inhibition by Thiophene-2-carboximidamides.

ABSTRACT: The overproduction of nitric oxide in the brain by neuronal nitric oxide synthase (nNOS) is associated with a number of neurodegenerative diseases. Although inhibiting nNOS is an important therapeutic goal, it is important not to inhibit endothelial NOS (eNOS) because of the critical role played by eNOS in maintaining vascular tone. While it has been possible to develop nNOS selective aminopyridine inhibitors, many of the most potent and selective inhibitors exhibit poor bioavailability properties. Our group and others have turned to more biocompatible thiophene-2-carboximidamide (T2C) inhibitors as potential nNOS selective inhibitors. We have used crystallography and computational methods to better understand how and why two commercially developed T2C inhibitors exhibit selectivity for hu

SUBMITTER: Li H 

PROVIDER: S-EPMC6282162 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature