生物活性

• 靶点

  PPARδ EC50:175nM

  PPARα EC50:45Nm

• 描述Elafibranor, also known as GFT505, is a dual agonist of peroxisome proliferator-activated receptor-α/δ (PPAR-α/δ) with EC50 values of 45 and 175nM, respectively^[3]. Treatment of hApoE2 KI mice with Elafibranor (30 mg/kg/day) for 6 weeks significantly decreased the plasma concentrations of total cholesterol, triglycerides, and free fatty acids, and greatly increased the level of high-density lipoprotein cholesterol compared to vehicle-treated group. In both hApoE2 KI and hApoE2 KI/PPAR‐α KO mice, Elafibranor treatment significantly reduced hepatic expressions of interleukin‐1β, tumor necrosis factor‐α, transforming growth factor‐β, and tissue inhibitor of metalloproteinase-2. Methionine- and choline-deficient diet induced steatohepatitis in db/db mice, whereas supplementation with Elafibranor (1, 3, or 10 mg/kg/day) for 7 weeks reduced intrahepatic cholesterol and triglyceride content in a dose‐dependent manner. In SD rats concomitantly injected with CCl₄ and treated with Elafibranor (30 mg/kg/day) for 7 weeks, the fibrotic surface and hepatic collagen content were significantly decreased, and the number of macrophages and activated hepatic stellate cells were significantly reduced as compared to CCl₄ control group^[4].
• 作用机制Elafibranor is a PPAR-α/δ agonist that exhibits liver-protective effects in non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and liver fibrosis. It has also been shown to reduce fasting glucose and improve insulin sensitivity similar to PPAR-γ agonist rosiglitazone.
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01474161	Type 2 Diabetes ... more >> Diabetes Mellitus, Type 2 Metabolic Diseases Cardiovascular Diseases Obese Dyslipidemia Collapse <<	Phase 1	Completed	-	France ... more >> SGS Aster S.A.S. - Phase I Clinical Unit Paris, France, 75015 Collapse <<
  NCT01694849	Non-Alcoholic Steatohepatitis ... more >>(NASH) Collapse <<	Phase 2	Completed	-	-
  NCT01275469	Impaired Glucose Tolerance ... more >> Abdominal Obesity Collapse <<	Phase 2	Completed	-	France ... more >> Site n°31 Angers, France, 49000 Site n°32 Angers, France, 49000 Site n°36 Angers, France, 49000 Site n°37 Angers, France, 49000 Site n°34 Angers, France, 49100 Site n°35 Angers, France, 49100 Site n°39 Angers, France, 49100 Site n°17 Briollay, France, 49125 Site n°16 Cholet, France, 49300 Site n°19 Cholet, France, 49300 Site n°14 le MESNIL en VALLEE, France, 49410 Site n°10 Murs-erigne, France, 49610 Site n°12 Murs-erigne, France, 49610 Site n°2 Nantes, France, 44093 Site n°13 Parcay Les Pins, France, 49390 Site n°1 Paris, France, 75013 Site n°15 Segre, France, 49500 Site n°11 Thouars, France, 79100 Site n°30 Tierce, France, 49125 Site n°18 Vihiers, France, 49310 Collapse <<

• 更多
• 参考文献

• [1] Ratziu V, Harrison SA, et al. Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-α and -δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening. Gastroenterology. 2016 May;150(5):1147-1159.e5.

  [2] Liu ZM, Hu M, et al. Early investigational drugs targeting PPAR-α for the treatment of metabolic disease. Expert Opin Investig Drugs. 2015 May;24(5):611-21.

  [3] Liu ZM, Hu M, Chan P, Tomlinson B. Early investigational drugs targeting PPAR-α for the treatment of metabolic disease. Expert Opin Investig Drugs. 2015 May;24(5):611-21. doi: 10.1517/13543784.2015.1006359. Epub 2015 Jan 21. PMID: 25604802.

  [4] Staels B, Rubenstrunk A, Noel B, Rigou G, Delataille P, Millatt LJ, Baron M, Lucas A, Tailleux A, Hum DW, Ratziu V, Cariou B, Hanf R. Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology. 2013 Dec;58(6):1941-52. doi: 10.1002/hep.26461. Epub 2013 Oct 29. PMID: 23703580.