High-throughput screening identifies small molecule inhibitors of thioesterase superfamily member 1: Implications for the management of non-alcoholic fatty liver disease.

ABSTRACT:

Objective

Thioesterase superfamily member 1 (Them1) is a long chain acyl-CoA thioesterase comprising two N-terminal HotDog fold enzymatic domains linked to a C-terminal lipid-sensing steroidogenic acute regulatory transfer-related (START) domain, which allosterically modulates enzymatic activity. Them1 is highly expressed in thermogenic adipose tissue, where it functions to suppress energy expenditure by limiting rates of fatty acid oxidation, and is induced markedly in liver in response to high fat feeding, where it suppresses fatty acid oxidation and promotes glucose production. Them1^-/- mice are protected against non-alcoholic fatty liver disease (NAFLD), suggesting Them1 as a therapeutic target.

Methods

A high-throughput small molecule screen was performed to

SUBMITTER: Krumm CS 

PROVIDER: S-EPMC10663673 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature