Research Article Details
| Article ID: | A08900 |
| PMID: | 31948295 |
| Source: | Expert Opin Investig Drugs |
| Title: | Fibroblast growth factor (FGF)-21 based therapies: A magic bullet for nonalcoholic fatty liver disease (NAFLD)? |
| Abstract: | Introduction: Fibroblast growth factor (FGF) 21 is a member of the FGF19 sub-family of signaling molecules. They have been found to act at the localized paracrine/autocrine and systemic endocrine levels because of their extracellular matrix and co-receptor protein binding characteristics. While the molecule circulates systemically, it has specificity conferred by a co-factor binding protein β-Klotho which is preferentially expressed in hepatic and adipose tissues. This protein, in conjunction with the FGF receptor (FGFR), propagates the downstream effects of the growth factor signaling cascade, which has been linked to fat and glucose metabolism. FGF21 has been recognized as a possible pathway for the treatment of nonalcoholic fatty liver disease (NAFLD). Targeting of the FGF21/FGFR/β-Klotho pathway may halt or reverse hepatic fat infiltration, inflammation, and fibrosis.Areas covered: This article summarizes preclinical and clinical data on the efficacy and safety of two FGF21 agonist therapies in development.Expert opinion: Preclinical and clinical data justify further investigation of FGF21 agonist therapies for the treatment of NAFLD. However, issues including injection site reactions and possible effects on bone homeostasis mean that safety must be evaluated carefully. |
| DOI: | 10.1080/13543784.2020.1718104 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D414 | Efruxifermin | Biological drug | -- | Fibroblast growth factor receptor agonist | anti-fibrotic, improves metabolic status | Under clinical trials | Details |
| D046 | Pegbelfermin | Biological drug | DB15365 | FGF21 analog | Improve insulin resistance; Enhance lipid metabolism; Anti-fibrosis | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |