Elafibranor

Identification

Name
Elafibranor
Accession Number
DB05187
Type
Small Molecule
Groups
Investigational
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.

Structure
Thumb
Synonyms
Not Available
External IDs
GFT-505 / GFT505
Categories
UNII
2J3H5C81A5
CAS number
923978-27-2
Weight
Average: 384.49
Monoisotopic: 384.139530427
Chemical Formula
C22H24O4S
InChI Key
AFLFKFHDSCQHOL-IZZDOVSWSA-N
InChI
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+
IUPAC Name
2-{2,6-dimethyl-4-[(1E)-3-[4-(methylsulfanyl)phenyl]-3-oxoprop-1-en-1-yl]phenoxy}-2-methylpropanoic acid
SMILES
CSC1=CC=C(C=C1)C(=O)\C=C\C1=CC(C)=C(OC(C)(C)C(O)=O)C(C)=C1

Pharmacology

Indication

Investigated for use/treatment in atherosclerosis and diabetes mellitus type 2.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

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).

TargetActionsOrganism
UPeroxisome proliferator-activated receptor alphaNot AvailableHuman
UPeroxisome proliferator-activated receptor deltaNot AvailableHuman
UPeroxisome proliferator-activated receptor gammaNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
9864881
PubChem Substance
347827716
ChemSpider
8040573
ChEMBL
CHEMBL3707395
Wikipedia
Elafibranor

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentAtherogenic Dyslipidemia / Obesity, Abdominal1
2CompletedTreatmentImpaired Glucose Tolerance (IGT) / Obesity, Abdominal1
2CompletedTreatmentInsulin Resistance / Obesity, Abdominal1
2CompletedTreatmentNon-Alcoholic Steatohepatitis (NASH)1
2CompletedTreatmentType 2 Diabetes Mellitus1
2RecruitingTreatmentPrimary Biliary Cholangitis (PBC)1
3RecruitingTreatmentNonalcoholic Steatohepatitis (NASH) With Fibrosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000228 mg/mLALOGPS
logP4.6ALOGPS
logP5.87ChemAxon
logS-6.2ALOGPS
pKa (Strongest Acidic)4ChemAxon
pKa (Strongest Basic)-4.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.6 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity111.47 m3·mol-1ChemAxon
Polarizability43.14 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as retrochalcones. These are a form of normal chalcones that are structurally distinguished by the lack of oxygen functionalities at the C2'- and C6'-positions.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Linear 1,3-diarylpropanoids
Sub Class
Chalcones and dihydrochalcones
Direct Parent
Retrochalcones
Alternative Parents
Cinnamic acids and derivatives / Phenoxyacetic acid derivatives / Aryl ketones / Benzoyl derivatives / m-Xylenes / Phenol ethers / Phenoxy compounds / Thiophenol ethers / Styrenes / Alkyl aryl ethers
show 8 more
Substituents
Retrochalcone / Cinnamic acid or derivatives / Phenoxyacetate / M-xylene / Xylene / Benzoyl / Phenoxy compound / Aryl ketone / Phenol ether / Aryl thioether
show 23 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleyleth...
Gene Name
PPARA
Uniprot ID
Q07869
Uniprot Name
Peroxisome proliferator-activated receptor alpha
Molecular Weight
52224.595 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-lin...
Gene Name
PPARD
Uniprot ID
Q03181
Uniprot Name
Peroxisome proliferator-activated receptor delta
Molecular Weight
49902.99 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da

Drug created on October 21, 2007 16:24 / Updated on December 01, 2017 15:35