PPAR-α (IC50 = 45 nM); PPAR-δ (IC50 = 175 nM)
PPAR-α (specific IC₅₀/Ki/EC₅₀ values ) [1][2][3][4]
PPAR-δ (specific IC₅₀/Ki/EC₅₀ values ) [2][3][4]

Elafibranor (GFT505) is being developed as a dual agonist for PPAR-α and PPAR-δ to inhibit non-alcoholic fatty liver disease and type 2 diabetes. GFT1007, an active metabolite of elafibranor, exhibits strong agonist activity for PPAR-α and somewhat for PPAR-δ[1].

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Elafibranor (GFT505) restricts lipogenic and inflammatory responses in a human skin stem cell-derived NASH model; it reduces intracellular lipid accumulation, modulates NASH-specific gene expression, decreases caspase-3/7 activity, and lowers the expression and secretion of inflammatory markers (CCL2, CCL5, CCL7, CCL8, CXCL5, CXCL8, IL1a, IL6, IL11) via NFκB-mediated pathway [4]
Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism, and reduces inflammation in in vitro systems relevant to metabolic diseases [2][3]
Transcriptomics analyses confirm common modulated genes and overlapping gene classes between Elafibranor-treated in vitro NASH models and human NASH patients, verifying human relevance [4]

Elafibranor is well tolerated; however, it does result in a slight, reversible elevation in serum creatinine and neither weight gain nor cardiac events. In addition to lowering inflammation, elafibranor enhances lipid metabolism and glucose homeostasis[2]. Treatment with elafibranor (GFT505) improves plasma lipids and glucose regulation in diabetic db/db mice. With Elafibranor, hepatic expression of the major gluconeogenic enzymes fructose 1,6-bisphosphatase 1 (FBP1), PEPCK, and glucose 6-phosphatase (G6Pase) is significantly dose-dependently reduced. In monkeys, PPARγ-activating agonists do not cause cardiac side effects when elabranor is used[3].

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In intention-to-treat analysis, there was no significant difference between the elafibranor and placebo groups in the protocol-defined primary outcome. However, NASH resolved without fibrosis worsening in a higher proportion of patients in the 120-mg elafibranor group vs the placebo group (19% vs 12%; odds ratio = 2.31; 95% confidence interval: 1.02-5.24; P = .045), based on a post-hoc analysis for the modified definition. In post-hoc analyses of patients with nonalcoholic fatty liver disease activity score ≥4 (n = 234), elafibranor 120 mg resolved NASH in larger proportions of patients than placebo based on the protocol definition (20% vs 11%; odds ratio = 3.16; 95% confidence interval: 1.22-8.13; P = .018) and the modified definitions (19% vs 9%; odds ratio = 3.52; 95% confidence interval: 1.32-9.40; P = .013). Patients with NASH resolution after receiving elafibranor 120 mg had reduced liver fibrosis stages compared with those without NASH resolution (mean reduction of 0.65 ± 0.61 in responders for the primary outcome vs an increase of 0.10 ± 0.98 in nonresponders; P < .001). Liver enzymes, lipids, glucose profiles, and markers of systemic inflammation were significantly reduced in the elafibranor 120-mg group vs the placebo group. Elafibranor was well tolerated and did not cause weight gain or cardiac events, but did produce a mild, reversible increase in serum creatinine (effect size vs placebo: increase of 4.31 ± 1.19 μmol/L; P < .001). Conclusions: A post-hoc analysis of data from trial of patients with NASH showed that elafibranor (120 mg/d for 1 year) resolved NASH without fibrosis worsening, based on a modified definition, in the intention-to-treat analysis and in patients with moderate or severe NASH. However, the predefined end point was not met in the intention to treat population. Elafibranor was well tolerated and improved patients' cardiometabolic risk profile. ClinicalTrials.gov number: NCT01694849.[2]

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Elafibranor attenuated in vitro key features of NASH, and dramatically lowered lipid load as well as the expression and secretion of inflammatory chemokines, which in vivo are responsible for the recruitment of immune cells. This reduction in inflammatory response was NFκB-mediated. In summary, this human-relevant, in vitro system proved to be a sensitive testing tool for the investigation of novel anti-NASH compounds.[4]

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In db/db mice (diabetes model), Elafibranor reduces fasting glycaemia and HbA1c, improves insulin sensitivity, and decreases hepatic gluconeogenesis (correlating with reduced gluconeogenic gene expression) after up to 8 weeks of treatment; it shows comparable glucose-lowering effects to PPARγ agonist rosiglitazone and dual-PPARα/γ agonist aleglitazar [3]
In cynomolgus monkeys, 12-month administration of Elafibranor causes no echocardiographic or histological cardiac abnormalities, and no changes in haematological parameters or bone marrow differential cell counts [3]
In an international randomized double-blind placebo-controlled Phase II trial (NCT01694849) involving patients with NASH without cirrhosis:
- 120 mg/d Elafibranor for 52 weeks resolves NASH without fibrosis worsening in 19% of patients (vs 12% in placebo group) in intention-to-treat analysis (modified definition, P=0.045) [2]
- In patients with NAFLD activity score ≥4 (n=234), 120 mg/d Elafibranor achieves NASH resolution in 20% (protocol definition, P=0.018) and 19% (modified definition, P=0.013) of patients vs 11% and 9% in placebo group [2]
- Patients with NASH resolution after 120 mg/d Elafibranor show a mean reduction of 0.65 ± 0.61 in liver fibrosis stage (vs 0.10 ± 0.98 increase in non-responders, P<0.001) [2]
- Elafibranor 120 mg/d significantly reduces liver enzymes, lipids, glucose profiles, and systemic inflammation markers vs placebo [2]

Elafibranor is an agonist of PPARα/δ with EC50 values of 45 and 175 nM, in that order. As a dual PPAR-α/PPAR-δ agonist, GFT505 is being developed to treat non-alcoholic fatty liver disease and type 2 diabetes. GThe active metabolite of GFT505, GFT1007, exhibits strong agonist activity for PPAR-α and to a lesser degree for PPAR-δ.

hSKP-HPC cell culture and establishment of steatosis and NASH in vitro models [4]
hSKP were isolated from circumcision samples of young boys from 1 to 10 years old, after informed consent from the parents and approval of the medical ethical committee of the UZ Brussels. These cells were cultured and differentiated to hepatocyte-like cells (hSKP-HPC) as previously documented. Steatosis was mimicked in vitro by exposing hSKP-HPC (24 h) to insulin (100 nM) and glucose (4.5 mg/mL). NASH conditions were created by concurrent exposure (24 h) to sodium oleate (65 μM) and palmitic acid (45 μM) in combination with a pro-inflammatory (50 ng/mL tumour necrosis factor (TNF)-alpha  + 25 ng/mL interleukin (IL)-1β) and pro-fibrotic (8 ng/mL transforming growth factor (TGF)-β1) cytokine cocktail. Sodium oleate was complexed with 7% (w/v) bovine serum albumin (BSA) fatty acid-free. Palmitic acid and elafibranor were dissolved in dimethyl sulfoxide (DMSO). Cells were concomitantly exposed to NASH triggers and elafibranor (10 μM and 30 μM). Final concentrations of BSA and DMSO in all samples were 0.14% (w/v) and 0.15% (v/v), respectively (except for the determination of the sodium oleate and palmitic acid concentration (shown in Supplementary Fig. 1A and B), where 1.4% (w/v) BSA and 0.5% (v/v) DMSO were used, respectively).

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Antibody array for determination of cytokines and chemokines [4]
Fresh cell culture media of control samples and cells exposed to NASH inducers and elafibranor (10 μM and 30 μM) were collected for determining interleukin and chemokine secretion using a human cytokine antibody array (120 Targets) according to the manufacturer's protocol. Visualization of the hybridization spots was performed using a Chemidoc™ MP system. Image Lab 5.0 software was used for semi-quantitative data analysis (n = 5, except for hSKP-HPC NASH +elafibranor 30 μM: n = 3).

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Generate hepatic cells from human skin-derived precursors to establish an in vitro NASH model; expose cells to lipogenic factors (insulin, glucose, fatty acids) and pro-inflammatory factors (IL-1β, TNF-α, TGF-β) to induce NASH-like responses [4]
Treat the in vitro NASH model with Elafibranor; assess intracellular lipid accumulation, NASH-specific gene expression (via transcriptomics), caspase-3/7 activity, and secretion of inflammatory markers (CCL2, CCL5, etc.) to evaluate drug efficacy [4]
Perform NFκB pathway analysis to confirm the mechanism of Elafibranor-mediated reduction in inflammatory responses [4]

hApoE2 KI and hApoE2 KI/PPAR-α KO mice
30 mg/kg
oral gavage

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Researchers report here the efficacy and safety of GFT505, a novel liver-targeted peroxisome proliferator-activated receptor alpha/delta (PPARα/δ) agonist, in the db/db mouse model of diabetes. Mice were treated with vehicle, GFT505, PPARγ agonist rosiglitazone or dual-PPARα/γ agonist aleglitazar for up to 8 weeks. All compounds comparably reduced fasting glycaemia and HbA1c and improved insulin sensitivity. The glucose-lowering effect of GFT505 was associated with decreased hepatic gluconeogenesis, correlating with reduced expression of gluconeogenic genes. In contrast with the PPARγ-activating drugs, treatment with GFT505 did not affect heart weight and did not increase plasma adiponectin concentrations. This absence of cardiac effects of GFT505 was confirmed after 12 months of administration in cynomolgus monkeys, by the absence of echocardiographic and histological findings. Moreover, long-term GFT505 administration to monkeys induced no change in haematological parameters or in bone marrow differential cell counts. Compared to PPARγ-activating drugs, the dual-PPARα/δ agonist GFT505 therefore shows an improved benefit/risk ratio, treating multiple features of type 2 diabetes without inducing the cardiac side-effects associated with PPARγ activation.[3]

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Patients with NASH without cirrhosis were randomly assigned to groups given elafibranor 80 mg (n = 93), elafibranor 120 mg (n = 91), or placebo (n = 92) each day for 52 weeks at sites in Europe and the United States. Clinical and laboratory evaluations were performed every 2 months during this 1-year period. Liver biopsies were then collected and patients were assessed 3 months later. The primary outcome was resolution of NASH without fibrosis worsening, using protocol-defined and modified definitions. Data from the groups given the different doses of elafibranor were compared with those from the placebo group using step-down logistic regression, adjusting for baseline nonalcoholic fatty liver disease activity score.[2]

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Treat db/db mice (diabetes model) with vehicle, Elafibranor, rosiglitazone, or aleglitazar for up to 8 weeks; monitor fasting glycaemia, HbA1c, insulin sensitivity, hepatic gluconeogenesis, and gluconeogenic gene expression [3]
Administer Elafibranor to cynomolgus monkeys for 12 months; perform echocardiographic and histological examinations of the heart, and analyze haematological parameters and bone marrow differential cell counts [3]

Absorption
After once-daily administration, elafibranor and its major active metabolite GFT1007 reached steady state in 7 and 14 days, respectively. At steady state, the mean (standard deviation) Cmax of elafibranor was 802 (443) ng/mL, and the mean (standard deviation) Cmax of GFT1007 was 2058 (459) ng/mL. The mean (standard deviation) AUC of elafibranor was 3758 (1749) ng·h/mL, and the mean (standard deviation) AUC of GFT1007 was 11985 (7149) ng·h/mL. In patients with PBC, after once-daily administration of 80 mg, the median time to peak plasma concentration (Tmax) of elafibranor and GFT1007 was 1.25 hours (range: 0.5–2 hours). Compared to the fasting state, when taken with a high-fat, high-calorie meal, the time to peak concentration (Tmax) of elafibranor was delayed by 30 minutes, and the time to peak concentration of GFT1007 was delayed by 1 hour. After eating, the mean peak concentration (Cmax) and area under the curve (AUC) of elafibranor decreased by 50% and 15%, respectively, while the mean peak concentration (Cmax) of GFT1007 decreased by 30%, but the AUC was unaffected compared to the fasting state. This difference was not clinically significant.
Elimination Route
In healthy subjects, following a single oral dose of 120 mg (1.5 times the recommended dose) of radiolabeled elafibranor at 14C, approximately 77.1% of the dose was recovered in feces, primarily as elafibranor (56.7% of the administered dose) and its major metabolite GFT1007 (6.08% of the administered dose). Approximately 19.3% of the drug was recovered in the urine, primarily as the glucuronide conjugate GFT3351 (11.8% of the administered dose). Only trace amounts of unmetabolized elafibranor or GFT1007 were detected in the urine. Following oral administration of elafibranor to rats, 60% of the drug was excreted via bile, suggesting that elafibranor may also be excreted via bile in humans.
Volume of Distribution
The mean apparent volume of distribution (Vd/F) after a single fasting administration of 80 mg elafibranor to healthy subjects was 4731 L.
Clearance
The mean apparent total clearance (CL/F) after a single fasting administration of 80 mg elafibranor was 50.0 L/h.
Protein Binding
Elafibranor and GFT1007 bind to approximately 99.7% of plasma proteins, primarily serum albumin. Metabolites/Metabolites
Elafibranor is extensively metabolized to a major active metabolite, GFT1007, the chemical structure of which is not yet fully understood. At steady state, the mean systemic exposure (AUC) of GFT1007 is 3.2 times that of elafibranor. GFT3351, an acylglucuronide conjugate, is the major inactive metabolite, composed of four stereoisomers. In vitro studies have shown that elafibranor is metabolized to GFT1007 by the cytoplasmic enzyme 15-ketoprostaglandin 13-Δ reductase (PTGR1). Elafibranor is also metabolized via CYP2J2, UGT1A3, UGT1A4, and UGT2B7. GFT1007 is further metabolized via CYP2C8, UGT1A3, and UGT2B7.
Biological Half-Life
After a single 80 mg dose on an empty stomach, the median elimination half-life of elafibranor is 70.2 hours (range 37.1 to 92.2 hours), and the median elimination half-life of the major active metabolite GFT1007 is 15.4 hours (range 9.39 to 21.7 hours).

Hepatotoxicity
In pre-registration clinical trials, elafibranor was found to reduce serum transaminase and alkaline phosphatase levels in a significant proportion of patients with primary biliary cholangitis (PBC). In preliminary dose-exploration studies in healthy volunteers, elevated ALT and AST levels exceeding the upper limit of normal (ULN) by more than 5 times were found to be dose-related, occurring in approximately one-third of subjects receiving daily doses exceeding 120 mg. In contrast, in clinical trials of elafibranor at a daily dose of 80 mg in patients with non-alcoholic steatohepatitis (NASH) and PBC, only 1% to 2% of patients experienced ALT elevations exceeding 5 times the ULN, typically occurring within the first few months of treatment and resolving spontaneously without interruption of treatment or the development of jaundice or other symptoms. Careful evaluation of the ALT elevation cases concluded that three cases were likely due to drug-induced damage: two out of 138 PBC patients and one out of 1433 NASH patients. Among patients who developed myalgia and elevated CPK during elafibranor treatment, one patient with a history of cirrhosis and concurrent statin therapy developed jaundice (5.5 mg/dL), elevated ALT (300 U/L) and AST (828 U/L), along with rhabdomyolysis (CPK 12,647 U/L), subsequently leading to hepatic decompensation. elafibranor treatment may also increase the incidence of gallstones and cholecystitis. Other PPARα (fenofibrate, bezafibrate) and PPARγ (pioglitazone, rosiglitazone) agonists are known to cause rare drug-induced liver injury. Probability score: E (Unproven but suspected rare cause of clinically significant liver injury). Elafibranor was well tolerated in the Phase II clinical trial; it did not cause weight gain or cardiac events, but it did cause a slight, reversible increase in serum creatinine (effect size compared to placebo: 4.31 ± 1.19 μmol/L, P < 0.001) [2] Unlike PPARγ activators (rosiglitazone, agliflozin), Elafibranor did not affect heart weight or increase plasma adiponectin concentration in db/db mice [3] Long-term (12 months) administration of Elafibranor to cynomolgus monkeys did not show cardiotoxicity, hematological abnormalities or myelotoxicity [3]

[1]. Early investigational drugs targeting PPAR-α for the treatment of metabolic disease.Expert Opin Investig Drugs. 2015 May;24(5):611-21.

[2]. 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.

[3]. The dual peroxisome proliferator-activated receptor 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. 2014 Nov;11(6):440-7.

[4]. Elafibranor restricts lipogenic and inflammatory responses in a human skin stem cell-derived model of NASH. Pharmacol Res. 2019 Jun:144:377-389.

Elafibranor (code name GFT505) is a multimodal, multi-effect drug for the treatment of atherogenic dyslipidemia in overweight patients with or without diabetes. It is an oral medication that acts on three subtypes of peroxisome proliferator-activated receptor (PPAR) (PPARα, PPARγ, and PPARδ), with a more significant effect on PPARα. As of February 2016, Elafibranor had completed eight clinical trials and was currently undergoing one Phase III clinical trial. Elafibranor is an oral peroxisome proliferator-activated receptor agonist used in combination with ursodeoxycholic acid for the treatment of primary biliary cholangitis. Rarely, elevated liver enzymes have been observed during Elafibranor treatment, but there is no conclusive evidence linking it to clinically significant liver damage with jaundice. Drug Indications It has been investigated for the treatment of atherosclerosis and type 2 diabetes.
Treatment of primary biliary cholangitis
Treatment of non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH)
Mechanism of Action
GFT505 is an oral medication that acts on three subtypes of PPAR (PPARα, PPARγ, PPARδ), preferentially acting on PPARα. Its mechanism of action is complex. It can differentially recruit cofactors to nuclear receptors, leading to differential regulation of gene expression and biological effects. Therefore, identifying and analyzing the activity of selective nuclear receptor modulators (SNuRMs) is an effective method for screening innovative drug candidates with higher efficacy and fewer side effects. These multifunctional molecules have significant positive effects on obesity, insulin resistance and diabetes, atherosclerosis, inflammation, and the lipid triad (increasing high-density lipoprotein cholesterol, decreasing triglycerides and low-density lipoprotein cholesterol).
Introduction: Fibrates have been used for many years to treat dyslipidemia and have recently been shown to have anti-inflammatory effects. These are relatively weak PPAR-α agonists and do have some adverse effects. Novel compounds, selective PPAR modulators (SPPARMs), with stronger PPAR-α agonist activity, are currently under development. These drugs may offer advantages in treating dyslipidemia, insulin resistance, and non-alcoholic fatty liver disease (NAFLD). This review focuses on PPAR-α agonists or SPPARMs under development and describes their preclinical and early-stage clinical studies. Information was derived from a search of published literature and recent conference abstracts. Ongoing clinical trials were searched using the Clinicaltrials.gov database. Expert opinion: New drugs are still needed to treat atherosclerotic dyslipidemia. The highly potent and selective PPAR-α agonist K-877 has shown beneficial effects on atherosclerotic dyslipidemia and avoids some of the adverse effects of fibrates. The dual PPAR-α/PPAR-δ agonist GFT-505 has shown promising results in improving atherosclerotic dyslipidemia and insulin resistance and appears to be a potential candidate for the treatment of NAFLD. Long-term trials are needed to evaluate the safety and efficacy of these new drugs for cardiovascular and hepatic outcomes. [1]

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Non-alcoholic steatohepatitis (NASH) is characterized by hepatocellular steatosis with liver inflammation. Despite its global pandemic status, no anti-NASH drugs have been approved. This is partly due to the lack of effective tools for evaluating the efficacy of potential candidates, which has slowed the drug development process. This study describes the construction and application of a novel preclinical model of NASH using hepatocytes derived from human skin precursors. Exposing these cells to adipogenic factors (insulin, glucose, fatty acids) and pro-inflammatory factors (IL-1β, TNF-α, TGF-β) induced a typical non-alcoholic steatohepatitis (NASH) response, characterized by intracellular lipid accumulation, regulation of NASH-specific gene expression, enhanced caspase-3/7 activity, and expression and/or secretion of inflammatory markers (including CCL2, CCL5, CCL7, CCL8, CXCL5, CXCL8, IL-1α, IL-6, and IL-11). Transcriptomic analysis validated the human relevance of the proposed NASH model, revealing shared genes and gene classes between the in vitro system and NASH patients. Testing elafibranor (a promising anti-NASH compound currently undergoing phase III clinical trials) demonstrated the potential of this in vitro model. Elafibranor alleviated key features of NASH in vitro and significantly reduced lipid load and the expression and secretion of inflammatory chemokines responsible for recruiting immune cells in vivo. This reduction in inflammatory response was mediated by NFκB. In summary, this human-related in vitro system has proven to be a sensitive test tool for studying novel anti-NASH compounds. [4] Elafibranor (GFT505) is a dual PPAR-α/δ agonist and an investigational drug targeting the liver. [1][3] It is currently undergoing a Phase III clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). [4] Elafibranor has anti-diabetic effects in a type 2 diabetes model and can improve atherosclerotic dyslipidemia and insulin resistance, making it a potential candidate drug for the treatment of NAFLD/NASH. [1][3] Its mechanism of action involves the regulation of lipid metabolism, glucose homeostasis and inflammation, and its anti-inflammatory effect is achieved by inhibiting the NFκB pathway. [2][3][4]
In clinical trials, Elafibranor 120 mg/d showed superior efficacy compared to 80 mg/d; the pre-specified primary endpoint was not met in the intention-to-treat population, but post-hoc analysis showed significant benefit in specific patient subgroups.[2]
Pharmacodynamics
Elafibranor inhibits bile acid synthesis. Studies have also shown that it improves insulin sensitivity, glucose homeostasis, and lipid metabolism. In patients with primary biliary cholangitis (PBC), elafibranor reduced the average level of alkaline phosphatase (ALP). In vitro PPAR function assays showed that both elafibranor and GFT1007 activated PPARα (EC50 of 46 nM and 14 nM, respectively, and Emax of 56% and 61%, respectively, relative to the reference agonist). Elafibranor and GFT1007 exhibit approximately 3 to 8 times greater activation potency for PPAR-α than for PPAR-γ and PPAR-δ, respectively. Elafibranor is a dual agonist of peroxisome proliferator-activated receptor (PPAR) α and β/δ, acting by inhibiting bile acid synthesis. On June 10, 2024, Elafibranor received accelerated approval from the FDA for the treatment of primary biliary cholangitis (PBC). It also received EMA approval on September 23, 2024. Elafibranor is a peroxisome proliferator-activated receptor agonist. Its mechanism of action is as a peroxisome proliferator-activated receptor agonist and a cytochrome P450 3A4 inducer. Elafibranor is an orally bioavailable peroxisome proliferator-activated receptor (PPAR)-α (PPARα) and -δ (PPARδ) agonist that reduces bile acid activity. After oral administration, elafibranor and its main active metabolite GFT1007 target, bind to, and activate PPARα and PPARδ in the liver. This induces the expression of fibroblast growth factor 21 (FGF21) and downregulates CYP7A1 (a key enzyme responsible for the synthesis of bile acids from cholesterol). By reducing CYP7A1 expression, bile acid synthesis is reduced. This reduces bile toxicity and decreases inflammation and scarring associated with primary biliary cholangitis (PBC). Elafibranor is a small molecule drug, currently in Phase IV clinical trials (covering all indications), and was first approved in 2024 for cholangitis, with six other investigational indications.

C22H24O4S

384.49

384.139

C, 68.73; H, 6.29; O, 16.64; S, 8.34

923978-27-2

824932-88-9; 923978-27-2;

9864881

Light yellow to yellow solid powder

1.2±0.1 g/cm3

569.0±50.0 °C at 760 mmHg

297.9±30.1 °C

0.0±1.6 mmHg at 25°C

1.606

5.63

1

5

7

27

537

0

O(C1C(C)=CC(/C=C/C(C2C=CC(SC)=CC=2)=O)=CC=1C)C(C)(C)C(=O)O

AFLFKFHDSCQHOL-IZZDOVSWSA-N

InChI=1S/C22H24O4S/c1-14-12-16(13-15(2)20(14)26-22(3,4)21(24)25)6-11-19(23)17-7-9-18(27-5)10-8-17/h6-13H,1-5H3,(H,24,25)/b11-6+

2-[2,6-dimethyl-4-[(E)-3-(4-methylsulfanylphenyl)-3-oxoprop-1-enyl]phenoxy]-2-methylpropanoic acid

Elafibranor; 923978-27-2; 824932-88-9; Iqirvo; 2J3H5C81A5; 923978-27-2; GFT505; GFT-505; 824932-88-9; Elafibranor(GFT505); Elafibranor [INN]; Elafibranor [USAN]; GFT505; Elafibranor; GFT 505

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 2.87 mg/mL (7.46 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.17 mg/mL (5.64 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.17 mg/mL (5.64 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 4: ≥ 2.17 mg/mL (5.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.

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Solubility in Formulation 5: ≥ 2.17 mg/mL (5.64 mM)(saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)