Identification of protein partners for small molecules reshapes the understanding of nonalcoholic steatohepatitis and drug discovery

Nonalcoholic steatohepatitis (NASH) is the severe subtype of nonalcoholic fatty diseases (NAFLD) with few options for treatment. Patients with NASH exhibit partial responses to the current therapeutics and adverse effects. Identification of the binding proteins for the drugs is essential to understanding the mechanism and adverse effects of the drugs and fuels the discovery of potent and safe drugs. This paper aims to critically discuss recent advances in covalent and noncovalent approaches for identifying binding proteins that mediate NASH progression, along with an in-depth analysis of the mechanisms by which these targets regulate NASH.