ELAFIBRANOR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H24O4S
Molecular Weight	384.489
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CSC1=CC=C(C=C1)C(=O)\C=C\C2=CC(C)=C(OC(C)(C)C(O)=O)C(C)=C2

InChI

InChIKey=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+

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26874076 | http://www.genfit.com/pipeline/elafibranor/ | https://www.ncbi.nlm.nih.gov/pubmed/25604802

Elafibranor (GFT505) is an agonist of the peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-δ. GFT505 has an active metabolite, GFT1007, and both have potent agonist activity for PPAR-a and to a lesser extent for PPAR-d. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. Elafibranor (GFT505) reverses nonalcoholic steatohepatitis (NASH) to prevent fibrosis progression. With an outstanding safety and tolerance profile, elafibranor provides NASH patients with needed cardio-protective benefits. Elafibranor is currently being evaluated in the clinical Phase 3 study RESOLVE-IT. The safety profile of GFT505 from the completed clinical trials appears satisfactory with no indication of PPAR-g agonist effects such as edema or body weight gain.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Peroxisome proliferator-activated receptor alpha 62 Target ID: CHEMBL239 Sources: http://adisinsight.springer.com/drugs/800025107 \| https://www.ncbi.nlm.nih.gov/pubmed/25604802	Agonist 2752		45.0 nM [EC50]
Peroxisome proliferator-activated receptor delta 30 Target ID: CHEMBL3979 Sources: http://adisinsight.springer.com/drugs/800025107 \| https://www.ncbi.nlm.nih.gov/pubmed/25604802	Agonist 2752		175.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Nonalcoholic steatohepatitis (NASH) with fibrosis 1 Sources: https://clinicaltrials.gov/ct2/show/NCT02704403 http://adisinsight.springer.com/drugs/800025107	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
385.216 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT03883607	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELAFIBRANOR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: UNKNOWN
658.054 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT03883607	120 mg 1 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELAFIBRANOR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
973.301 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT03883607	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELAFIBRANOR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: UNKNOWN
1457.728 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT03883607	120 mg 1 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELAFIBRANOR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
34.17 h CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT03883607	80 mg 1 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELAFIBRANOR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: UNKNOWN
37.62 h CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT03883607	120 mg 1 times / day multiple, oral dose: 120 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ELAFIBRANOR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
120 mg 1 times / day multiple, oral Highest studied dose Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26874076	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26874076	Other AEs: Renal failure unspecified, Renal impairment... Other AEs: Renal failure unspecified (4.49%) Renal impairment (2.25%) Sources: https://pubmed.ncbi.nlm.nih.gov/26874076

AEs

AE	Significance	Dose	Population
Renal impairment	2.25%	120 mg 1 times / day multiple, oral Highest studied dose Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26874076	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26874076
Renal failure unspecified	4.49%	120 mg 1 times / day multiple, oral Highest studied dose Dose: 120 mg, 1 times / day Route: oral Route: multiple Dose: 120 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26874076	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26874076

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00GURI	https://www.1pchem.com/search?query=1P00GURI
A2B Chem	AH85566	http://a2bchem.com/prod/AH85566
AChemBlock	M22590	http://www.achemblock.com/catalogsearch/result/?q=M22590
Angene	AGN-PC-0VZE76	http://www.angenechemical.com/productshow/AGN-PC-0VZE76.html
AstaTech	40105	http://astatechinc.com/CPSResult.php?CRNO=40105
Axon MedChem	2727	https://www.axonmedchem.com/product/2727
BLD Pharm	BD318020	http://www.bldpharm.com/search/Search.html?keyword=BD318020
Chem Scene	CS-5522	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5522
ChemShuttle	169450	https://www.chemshuttle.com/catalogsearch/result/?q=169450
Combi-Blocks	QV-4242	http://www.combi-blocks.com/cgi-bin/find.cgi?QV-4242
eMolecules	195056009	https://orderbb.emolecules.com/search/#?query=195056009
eMolecules	303200536	https://orderbb.emolecules.com/search/#?query=303200536
eMolecules	76742194	https://orderbb.emolecules.com/search/#?query=76742194
eNovation Chemicals	D548292	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D548292&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A757	http://www.excenen.com/searchresultlist.php?id=EX-A757
Hairui	ELSA047	http://www.hairuichem.com/en/product/search.do?q=ELSA047
KeyOrganics	AS-57112	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-57112
Lab Network	LN01344126	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01344126
mcule	MCULE-1422976695	https://mcule.com/MCULE-1422976695/
mcule	MCULE-7792676406	https://mcule.com/MCULE-7792676406/
MedChem Express	HY-16737	https://www.medchemexpress.com/search.html?q=HY-16737&ft=&fa=&fp=
Molnova	M16620	https://www.molnova.com/en/serch-list.html?keywords=M16620
MolPort	MolPort-044-649-379	https://www.molport.com/shop/molecule-link/MolPort-044-649-379
MuseChem	I005500	https://www.musechem.com/product/I005500.html
ShangHai Biochempartner	BCP19067	http://www.biochempartner.com/search_BCP19067
TargetMol	T4408	https://www.targetmol.com/search?keyword=T4408
Toronto Research Chemicals	G368870	https://www.trc-canada.com/product-detail/?CatNum=G368870

PubMed

Title	Date	PubMed
Activation of intestinal peroxisome proliferator-activated receptor-α increases high-density lipoprotein production.	2013 Aug	22843443
Early investigational drugs targeting PPAR-α for the treatment of metabolic disease.	2015 May	25604802
Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-α and -δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening.	2016 May	26874076

Patents

Sample Use Guides

In Vivo Use Guide

Nonalcoholic Steatohepatitis (NASH) With Fibrosis :Coated tablets dosed at 120mg Elafibranor; oral administration; one tablet per day before breakfast with a glass of water.

Route of Administration: Oral

In Vitro Use Guide

Human jejunal biopsies were treated with Elafibranor (1uM) for 18h. Elafibranor (1uM) increased mRNA levels of fatty-acid-oxidation genes including Carnitine-Palmitoyl-Transferase-1 (CPT-1A), ACOX1 and long-chain Acyl-CoA synthetase family member 5 (ACSL5).

Name

Type

Language

elafibranor [INN]

Preferred Name

English

ELAFIBRANOR

Official Name

English

Elafibranor [WHO-DD]

Common Name

English

ELAFIBRANOR [USAN]

Common Name

English

IQIRVO

Brand Name

English

GFT505

Code

English

PROPANOIC ACID, 2-(2,6-DIMETHYL-4-((1E)-3-(4-(METHYLTHIO)PHENYL)-3-OXO-1-PROPEN-1-YL)PHENOXY)-

Systematic Name

English

PROPANOIC ACID, 2-(2,6-DIMETHYL-4-(3-(4-(METHYLTHIO)PHENYL)-3-OXO-1-PROPEN-1-YL)PHENOXY)-2-METHYL-

Systematic Name

English

GFT-505

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

693919