AUTHOR=Cheng Hao , Wang Xiao-Bo , Zhi Ying , Liu Bo , Liu Na , Li Meng-Jun , Mu Yan-Ling 

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

JOURNAL=Frontiers in Chemistry

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.888587

DOI=10.3389/fchem.2022.888587

ISSN=2296-2646

ABSTRACT=Developing effective therapies and medicines to conquer Non-alcoholic steatohepatitis (NASH) is of great significance for public health and faced with major challenge. The activation of 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 results showed that liver microsomes stable and have not metabolized, the t1/2 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 its characteristics of high sensitivity, rapidity, good selectivity.