The Race to Bash NASH: Emerging Targets and Drug Development in a Complex Liver Disease

J Med Chem. 2020 May 28;63(10):5031-5073. doi: 10.1021/acs.jmedchem.9b01701. Epub 2020 Jan 29.


Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD) characterized by liver steatosis, inflammation, and hepatocellular damage. NASH is a serious condition that can progress to cirrhosis, liver failure, and hepatocellular carcinoma. The association of NASH with obesity, type 2 diabetes mellitus, and dyslipidemia has led to an emerging picture of NASH as the liver manifestation of metabolic syndrome. Although diet and exercise can dramatically improve NASH outcomes, significant lifestyle changes can be challenging to sustain. Pharmaceutical therapies could be an important addition to care, but currently none are approved for NASH. Here, we review the most promising targets for NASH treatment, along with the most advanced therapeutics in development. These include targets involved in metabolism (e.g., sugar, lipid, and cholesterol metabolism), inflammation, and fibrosis. Ultimately, combination therapies addressing multiple aspects of NASH pathogenesis are expected to provide benefit for patients.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / chemistry
  • Anticholesteremic Agents / metabolism
  • Drug Delivery Systems / methods
  • Drug Delivery Systems / trends*
  • Drug Development / methods
  • Drug Development / trends*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / metabolism
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / physiology
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / epidemiology
  • Metabolic Syndrome / metabolism
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Obesity / drug therapy
  • Obesity / epidemiology
  • Obesity / metabolism
  • PPAR gamma / agonists
  • PPAR gamma / chemistry
  • Protein Structure, Tertiary


  • Anticholesteremic Agents
  • Hypoglycemic Agents
  • PPAR gamma