Investigational Drug Details
| Drug ID: | D119 |
| Drug Name: | Elafibranor |
| Synonyms: | Elafibranor |
| Type: | Chemical drug |
| DrugBank ID: | DB05187 |
| DrugBank Description: | Elafibranor (code name GFT505) is a multimodal and pluripotent medication for treatment of atherogenic dyslipidemia for an overweight patient with or without diabetes. It is an oral treatment that acts on the 3 sub-types of PPAR (PPARa, PPARg, PPARd) with a preferential action on PPARa. As of February 2016, elafibranor has completed 8 clinical trials and a phase III is in progress. |
| PubChem ID: | 9864881 |
| CasNo: | 923978-27-2 |
| Repositioning for NAFLD: | No |
| SMILES: | CC1=C(OC(C)(C(O)=O)C)C(C)=CC(/C([H])=C([H])/C(C2=CC=C(SC)C=C2)=O)=C1 |
| Structure: |
|
| InChiKey: | AFLFKFHDSCQHOL-IZZDOVSWSA-N |
| Molecular Weight: | 384.497 |
| DrugBank Targets: | Peroxisome proliferator-activated receptor alpha; Peroxisome proliferator-activated receptor delta; Peroxisome proliferator-activated receptor gamma |
| DrugBank MoA: | GFT505 is an oral treatment that acts on the 3 sub-types of PPAR (PPARa, PPARg, PPARd) with a preferential action on PPARa. It has a sophisticated mechanism of action. It is able to differentially recruit cofactors to the nuclear receptor, which subsequently lead to differential regulation of genes and biological effect. Therefore, the ability to identify and profile the activity of selective nuclear receptor modulator (SNuRMs) is a powerful approach to select innovative drug candidates with improved efficacy and diminished side effects. These pluripotent and multimodal molecules have significant positive effects on obesity, insulin-resistance and diabetes, atherosclerosis, inflammation, and the lipid triad (increasing of HDL cholesterol, lowering of triglycerides and LDL cholesterol). |
| DrugBank Pharmacology: | -- |
| DrugBank Indication: | Investigated for use/treatment in atherosclerosis and diabetes mellitus type 2. |
| Targets: | PPARA; PPARD; PPARG |
| Therapeutic Category: | Anti-inflammatory |
| Clinical Trial Progress: | Phase 3 terminated (NCT02704403: Study did not meet the predefined primary surrogate efficacy endpoint, no safety issues identified.) |
| Latest Progress: | Failed in clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0002 | NCT03953456 | Phase 2 | Terminated | No Results Available | August 16, 2019 | August 31, 2020 | Details |
| L0207 | NCT03883607 | Phase 2 | Terminated | Has Results | June 25, 2019 | October 28, 2021 | Details |
| L0322 | NCT02704403 | Phase 3 | Terminated | No Results Available | March 2016 | November 30, 2020 | Details |
| L0592 | EUCTR2015-005385-38-BE | Phase 3 | Not Recruiting | No Results Available | 29/01/2016 | 16 November 2020 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name | |
|---|---|---|---|---|---|---|---|
| T03 | Peroxisome proliferator-activated receptor alpha | PPARA | agonist | Nuclear hormone receptor | Q07869 | PPARA_HUMAN | Details |
| T04 | Peroxisome proliferator-activated receptor delta | PPARD | agonist | Nuclear hormone receptor | Q03181 | PPARD_HUMAN | Details |
| T05 | Peroxisome proliferator-activated receptor gamma | PPARG | agonist | Nuclear hormone receptor | P37231 | PPARG_HUMAN | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A01204 | 34829876 | Biomedicines | Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers. | Details |
| A02030 | 34526653 | Commun Biol | Modelling human liver fibrosis in the context of non-alcoholic steatohepatitis using a microphysiological system. | Details |
| A02443 | 34370218 | Clin J Gastroenterol | Efficacy of elafibranor in patients with liver abnormalities especially non-alcoholic steatohepatitis: a systematic review and meta-analysis. | Details |
| A03482 | 33987427 | Ann Transl Med | Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH)-related liver fibrosis: mechanisms, treatment and prevention. | Details |
| A04016 | 33788377 | Liver Int | Elafibranor and liraglutide improve differentially liver health and metabolism in a mouse model of non-alcoholic steatohepatitis. | Details |
| A04097 | 33761646 | Medicine (Baltimore) | The efficacy of novel metabolic targeted agents and natural plant drugs for nonalcoholic fatty liver disease treatment: A PRISMA-compliant network meta-analysis of randomized controlled trials. | Details |
| A04338 | 33658534 | Sci Rep | Beneficial effects of elafibranor on NASH in E3L.CETP mice and differences between mice and men. | Details |
| A04643 | 33553970 | Hepatol Commun | Human Nonalcoholic Steatohepatitis on a Chip. | Details |
| A04937 | 33444606 | Metabolism | Elafibranor improves diet-induced nonalcoholic steatohepatitis associated with heart failure with preserved ejection fraction in Golden Syrian hamsters. | Details |
| A05080 | 33385317 | J Dig Dis | Efficacy and safety of drugs for nonalcoholic steatohepatitis. | Details |
| A05119 | 33368954 | Diabetes Obes Metab | Pioglitazone and bariatric surgery are the most effective treatments for non-alcoholic steatohepatitis: A hierarchical network meta-analysis. | Details |
| A05245 | 33326461 | PLoS One | The pharmacodynamic and differential gene expression analysis of PPAR α/δ agonist GFT505 in CDAHFD-induced NASH model. | Details |
| A05376 | 33278029 | Pharmacotherapy | Emerging therapies for the treatment of nonalcoholic steatohepatitis: A systematic review. | Details |
| A05793 | 33115209 | Diabetes Metab J | Nonalcoholic Fatty Liver Disease: A Drug Revolution Is Coming. | Details |
| A07125 | 32613381 | Cell Biol Toxicol | Human hepatic in vitro models reveal distinct anti-NASH potencies of PPAR agonists. | Details |
| A07827 | 32343209 | Radiology | Advanced MRI of Liver Fibrosis and Treatment Response in a Rat Model of Nonalcoholic Steatohepatitis. | Details |
| A08327 | 32151660 | Metabolism | Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis. | Details |
| A08581 | 32052857 | Hepatology | New Drugs for NASH and HIV Infection: Great Expectations for a Great Need. | Details |
| A08799 | 31981449 | Clin Transl Sci | A 3-week nonalcoholic steatohepatitis mouse model shows elafibranor benefits on hepatic inflammation and cell death. | Details |
| A08933 | 31931543 | Z Gastroenterol | [What is the (right) target for non-alcoholic fatty liver disease (NAFLD)?] | Details |