A Pyridazinone Compound for Effectively Treating Non-alcoholic Steatohepatitis by Targeting THRβ

Abstract

Developing effective therapies and medicines to conquer nonalcoholic steatohepatitis (NASH) is of great significance for public health and is faced with a major challenge. The activation of the thyroid hormone receptor agonist THRβ could be regulated by target drugs that has brought huge potential to the treatment of NASH. In this work, pyridazinone compound YWS01125 was synthesized for the first time. In this study, an ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method for YWS01125 determination was established, and the pharmacokinetics of YWS01125 was evaluated. The half-life values (t1/2)of three different doses of YWS01125 was 189.12 ± 95.27, 152.64 ± 37.98, and 181.95 ± 64.25 min, respectively, and the tissue distribution studies demonstrated that YWS01125 was quickly distributed to various tissues. With successful application in the pharmacokinetics study of YWS01125, the UPLC-MS/MS method has shown characteristics of high sensitivity, rapidity, and good selectivity.