Research Article Details
| Article ID: | A49851 |
| PMID: | 35620160 |
| Source: | Chronic Dis Transl Med |
| Title: | Hepatic hormone FGF21 and its analogues in clinical trials. |
| Abstract: | Fibroblast growth factor 21 (FGF21) is a fasting or stress inducible metabolic hormone produced mainly in the liver. It plays important roles in regulating both glucose and lipid homeostasis via interacting with a heterodimeric receptor complex comprising FGF receptor 1 (FGFR1) and β-klotho (KLB). For the past decade, great effort has been made on developing FGF21 derivatives or specific FGF21 receptor agonists into therapeutic agents for various metabolic disorders including type 2 diabetes (T2D), obesity, and more importantly, nonalcoholic fatty liver disease (NAFLD). Here we have reviewed FGF21 gene and protein structures, its expression pattern, cellular signaling cascades that mediate FGF21 production and function. We have then summarized the six clinical trials utilizing four FGF21 analogues. Finally, two recent literatures on the development of GLP-1 and FGF21 dual agonists were presented briefly. |
| DOI: | 10.1016/j.cdtm.2021.08.005 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T20 | Fatty acid synthase | FASN | inhibitor | Enzyme | P49327 | FAS_HUMAN | Details |
| T28 | Fibroblast growth factor 21 | FGF21 | analogue | Secreted | Q9NSA1 | FGF21_HUMAN | Details |
| T06 | Glucagon-like peptide 1 receptor | GLP1R | agonist | GPCR | P43220 | GLP1R_HUMAN | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress |
|---|