| Identification | Back Directory | [Name]
Elafibranor(GFT505) | [CAS]
923978-27-2 | [Synonyms]
CS-2411
SureCN815512
elafibranor E
Elafibranor(GFT505)
GFT505(ELAFIBRANOR)
GFT505; GFT-505; GFT 505;
Elafibranor (GFT-505, Ph III)
ELAFIBRANOR;GF T505;GFT-505;GFT505
Elafibranor(GFT505) ISO 9001：2015 REACH
(E)-2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxoprop-1-en-1-yl)phenoxy)-2-methylpropanoic acid
2-[2,6-Dimethyl-4-[(1E)-3-[4-(methylthio)phenyl]-3-oxo-1-propen-1-yl]phenoxy]-2-methylpropanoic acid
Propanoic acid, 2-[2,6-dimethyl-4-[(1E)-3-[4-(methylthio)phenyl]-3-oxo-1-propen-1-yl]phenoxy]-2-methyl- | [Molecular Formula]
C22H24O4S | [MOL File]
923978-27-2.mol | [Molecular Weight]
384.49 |
| Chemical Properties | Back Directory | [Boiling point ]
569.0±50.0 °C(Predicted) | [density ]
1.21±0.1 g/cm3(Predicted) | [storage temp. ]
-20° | [solubility ]
Soluble in DMSO (up to at least 25 mg/ml). | [form ]
solid | [pka]
3.30±0.11(Predicted) | [color ]
Pale yellow | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month. |
| Hazard Information | Back Directory | [Description]
Elafibranor is an agonist of the peroxisome proliferator-activated receptors (PPAR) α and δ.1 It increases HDL secretion and expression of the lipid-related genes ABCA1, PLIN2, and ABHD5 in Caco-2/TC7 cells in a PPARα-dependent manner. Elafibranor (10 mg/kg) decreases levels of plasma triglycerides and total cholesterol while increasing plasma HDL and expression of Acox1, a PPARα target gene, in the liver of ApoE2-KI wild-type, but not PPARα knockout, mice fed a Western diet. However, PPARα knockout mice exhibit a decrease in plasma total and non-HDL cholesterol levels, indicating PPARδ has a role in these functions. Elafibranor (30 mg/kg) reduces diet-induced macro- and micro-steatosis in a PPARα-deficient mouse model of non-alcoholic steatohepatitis.2 It also reduces cholesterol and triglyceride accumulation as well as macrovesicular steatosis in the liver of insulin-resistant db/db mice fed the methionine-choline deficient (MCD) diet. Formulations containing elafibranor are under clinical investigation for the treatment of non-alcoholic steatohepatitis. | [Uses]
GFT-505 is a?dual?PPARα/δ agonist. Studies have shown that GFT-505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects. It may also be a potential new drug candidate for treating lipid and glucose disorders. | [Biological Functions]
Elafibranor (GFT505) is an agonist of peroxisome proliferator-activated receptor (PPAR) alpha and delta. EC50 values were 45 and 175 nM, respectively. GFT505 is being developed as a dual PPAR-α/PPAR-δ receptor agonist for the treatment of type 2 diabetes and nonalcoholic fatty liver disease. GFT1007 and GFT505 have an active metabolite, both with potent stimulant activity PPAR-α and to a lesser extent PPAR-δ. | [Biological Activity]
Elafibranor (GFT505) is an agonist of PPAR-alpha and PPAR-delta, improves insulin sensitivity, benefits glucose homeostasis, lipid metabolism and reduces inflammation. | [in vivo]
Elafibranor is well tolerated and does not cause weight gain or cardiac events, but does produce a mild, reversible increase in serum creatinine. Elafibranor improves glucose homeostasis, and lipid metabolism and reduces inflammation[2]. Elafibranor (GFT505) treatment improves glucose control and plasma lipids in diabetic db/db mice. A significant dose-dependent reduction of hepatic expression of the key gluconeogenic enzymes glucose 6-phosphatase (G6Pase), PEPCK, and fructose 1,6-bisphosphatase 1 (FBP1) is observed with Elafibranor. Elafibranor does not induce cardiac adverse effects of PPARγ-activating agonists in monkeys[3]. | [IC 50]
PPAR-α: 45 nM (EC50); PPAR-δ: 175 nM (EC50) | [References]
1) Cariou?et al.?(2011)?Effects of the New Dual PPARα/δ Agonist GFT505 on Lipid and Glucose Homeostasis in Abdominally Obese Patients With Combined Dyslipidemia or Impaired Glucose Metabolism; Diabetes Care?34?2008
2) Cariou?et al.?(2013)?Dual peroxisome proliferator receptor α/δ agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects; Diabetes Care?36?2923
3) Hanf?et al.?(2014)?The dual peroxisome proliferator-activated alpha/delta agonist GFT505 exerts anti-diabetic effects in db/db mice without peroxisome proliferator-activated receptor gamma-associated adverse cardiac effects.; Diab. Vasc. Dis. Res.?11?440
4) Staels?et al.?(2013)?Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha-delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis; Hepatology?58?1941
5) Ratziu?et al.?(2016)?Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-α and -δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening.; Gastroenterology.?39?2951
6) Boeckmans?et al. (2019)?Elafibranor restricts lipogenic and inflammatory responses in a human skin stem cell-derived model of NASH.; Pharmacol. Res.?114?377 |
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