Ontology highlight
ABSTRACT:
SUBMITTER: Brust R
PROVIDER: S-EPMC6224492 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Brust Richard R Shang Jinsai J Fuhrmann Jakob J Mosure Sarah A SA Bass Jared J Cano Andrew A Heidari Zahra Z Chrisman Ian M IM Nemetchek Michelle D MD Blayo Anne-Laure AL Griffin Patrick R PR Kamenecka Theodore M TM Hughes Travis S TS Kojetin Douglas J DJ
Nature communications 20181108 1
Small chemical modifications can have significant effects on ligand efficacy and receptor activity, but the underlying structural mechanisms can be difficult to predict from static crystal structures alone. Here we show how a simple phenyl-to-pyridyl substitution between two common covalent orthosteric ligands targeting peroxisome proliferator-activated receptor (PPAR) gamma converts a transcriptionally neutral antagonist (GW9662) into a repressive inverse agonist (T0070907) relative to basal ce ...[more]