Synthesis and preclinical testing of a selective beta-subtype agonist of thyroid hormone receptor ZTA-261.

ABSTRACT:

Background

Thyroid hormones (TH) regulate the basal metabolic rate through their receptors THRα and THRβ. TH activates lipid metabolism via THRβ, however, an excess amount of TH can lead to tachycardia, bone loss, and muscle wasting through THRα. In recent years, TH analogs that selectively bind to THRβ have gained attention as new agents for treating dyslipidemia and obesity, which continue to pose major challenges to public health worldwide.

Methods

We developed a TH analog, ZTA-261, by modifying the existing THRβ-selective agonists GC-1 and GC-24. To determine the THRβ-selectivity of ZTA-261, an in vitro radiolabeled TH displacement assay was conducted. ZTA-261 was intraperitoneally injected into a mouse model of high-fat diet-induced obesity, and its effectiveness in red

SUBMITTER: Nambo M 

PROVIDER: S-EPMC11303563 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature