Elucidation of an Allosteric Mode of Action for a Thienopyrazole RORγt Inverse Agonist.

ABSTRACT: The demand for allosteric targeting of nuclear receptors is high, but examples are limited, and structural information is scarce. The retinoic acid-related orphan receptor gamma t (RORγt) is an important transcriptional regulator for the differentiation of T helper 17 cells for which the first, and some of the most promising, examples of allosteric nuclear receptor modulation have been reported and structurally proven. In a 2015 patent, filed by the pharmaceutical company Glenmark, a new class of small molecules was reported that act as potent inverse agonists for RORγt. A compound library around the central thienopyrazole scaffold captured a clear structure-activity relationship, but the binding mechanism of this new class of RORγt modulators has not been elucidated. Using a combination o

SUBMITTER: de Vries RMJM 

PROVIDER: S-EPMC7187189 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature