Research Article Details
| Article ID: | A08580 |
| PMID: | 32053033 |
| Source: | Expert Opin Ther Targets |
| Title: | Emerging therapeutic targets for NASH: key innovations at the preclinical level. |
| Abstract: | Introduction: nonalcoholic steatohepatitis (NASH) is a globally emerging health problem, mainly caused by increasing trends in the prevalence of obesity and metabolic syndrome. Patients with NASH are mainly affected by cardiovascular risk and extrahepatic cancer, but a significant proportion of patients will develop advanced liver disease, eventually resulting in liver failure or hepatocellular carcinoma. Recent research has yielded a better understanding of the underlying mechanisms and potential targetability for drug development.Areas covered: This review focuses on the role of fructose metabolism, de novo lipogenesis (DNL), endoplasmic reticulum (ER) stress, NLRP3 inflammasome, bone morphogenetic protein (BMP) signaling and platelets in the pathophysiology of NASH. We discuss the suitability of these substrates for targeting liver disease as well as cardiovascular health in patients with NASH. A non-systematic literature search was performed on PubMed and ClinicalTrials.gov.Expert opinion: Targeting fructose metabolism, DNL, ER stress, NLRP3 inflammasome, BMP signaling and platelets are promising therapeutic strategies, warranting further preclinical and clinical investigation. The discussed approaches might not only benefit liver-related outcomes but improve cardiovascular disease as well. Amidst the euphoria of advances in drug development for NASH, parallel endeavors need to address the underlying causes of obesity and metabolic syndrome to prevent NASH. |
| DOI: | 10.1080/14728222.2020.1728742 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S07 | Anti-lipogenesis | de novo lipogenesis; de novo lipogenesis; DNL; anti-lipogenic mechanisms; adipogenesis; anti-obesity | stearoyl-CoA desaturase 1 (SCD-1); Acetyl-coenzyme carboxylase; acyl-CoA carboxylase inhibitor (ACC inhibitor); stearoyl Coenzyme A desaturase inhibitor (SCD inhibitor); THR-beta selective agonist; DGAT2 inhibitor; FASN inhibitor | Aramchol; Firsocostat (GS-0976); VK-2809; ION 224 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |