Lanifibranor

Summary

Lanifibranor (CHEMBL4091374) is a phase-3 clinical-stage small molecule targeting PPARA, PPARD, and PPARG; indicated across 3 conditions including metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 3 (PPARA, PPARD, PPARG)
• Indications: 3 conditions
• Clinical trials: 7
• Chemistry: 434.9 Da · C19H15ClN2O4S2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4091374
Name	Lanifibranor
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	68677842
Molecular formula	C19H15ClN2O4S2
Molecular weight	434.9
InChIKey	OQDQIFQRNZIEEJ-UHFFFAOYSA-N

SMILES: C1=CC2=C(C=C1S(=O)(=O)N3C4=C(C=C(C=C4)Cl)C=C3CCCC(=O)O)SC=N2

IUPAC name: 4-[1-(1,3-benzothiazol-6-ylsulfonyl)-5-chloroindol-2-yl]butanoic acid

Also known as: IVA-337, Iva337, IVA337, Lanifibranor, LANIFIBRANOR

Patent coverage: 348 distinct patent families (992 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 892 (90%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
PPARA	Peroxisome proliferator-activated receptor-α	Agonist	5.81	0.7%	Q07869
PPARD	Peroxisome proliferator-activated receptor-β/δ	Agonist	6.06	0.6%	Q03181
PPARG	Peroxisome proliferator-activated receptor-γ	Agonist	6.69	2.6%	P37231

Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: Peroxisome proliferator-activated receptor alpha, Peroxisome proliferator-activated receptor gamma, Peroxisome proliferator-activated receptor alpha, Peroxisome proliferator-activated receptor delta, Peroxisome proliferator-activated receptor gamma, Peroxisome proliferator-activated receptor delta.

Bioactivity

ChEMBL activities: 26 potent at pChembl ≥ 5 of 26 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P37238	6.7	EC50	202	nM	CHEMBL_ACT_18109086
PPARG	6.69	EC50	206	nM	CHEMBL_ACT_18108993
PPARG	6.68	EC50	210	nM	CHEMBL_ACT_25110716
PPARG	6.68	EC50	210	nM	CHEMBL_ACT_26335930
P23204	6.44	EC50	366	nM	CHEMBL_ACT_18109082
PPARG	6.25	EC50	558.9	nM	CHEMBL_ACT_24405103
PPARG	6.22	EC50	600	nM	CHEMBL_ACT_25830134
PPARG	6.14	EC50	727	nM	CHEMBL_ACT_18109116
PPARD	6.06	EC50	866	nM	CHEMBL_ACT_18108929
PPARD	6.06	EC50	870	nM	CHEMBL_ACT_25110715
PPARD	6.05	EC50	900	nM	CHEMBL_ACT_26335931
PPARG	5.94	EC50	1140	nM	CHEMBL_ACT_18109112
PPARG	5.83	EC50	1484	nM	CHEMBL_ACT_18109118
PPARA	5.82	EC50	1500	nM	CHEMBL_ACT_25110705
PPARA	5.81	EC50	1537	nM	CHEMBL_ACT_18108844
P35396	5.81	EC50	1560	nM	CHEMBL_ACT_18109084
PPARG	5.72	EC50	1917	nM	CHEMBL_ACT_18109120
PPARD	5.54	EC50	2900	nM	CHEMBL_ACT_25830095
PPARD	5.53	EC50	2962	nM	CHEMBL_ACT_24405097
PPARA	5.51	EC50	3060	nM	CHEMBL_ACT_24405050
PPARA	5.5	EC50	3200	nM	CHEMBL_ACT_25830055
PPARG	5.49	EC50	3208	nM	CHEMBL_ACT_18109122
PPARG	5.49	EC50	3274	nM	CHEMBL_ACT_18109125
PPARG	5.47	EC50	3408	nM	CHEMBL_ACT_18109126
PPARG	5.39	EC50	4097	nM	CHEMBL_ACT_18109114
PPARG	5.39	EC50	4111	nM	CHEMBL_ACT_18109124

Target pathways

Aggregated over 3 target gene(s): PPARA, PPARD, PPARG.

Top Reactome pathways

18 total, by targets touching each:

Pathway	Targets	Genes
Nuclear Receptor transcription pathway	3	PPARA, PPARD, PPARG
PPARA activates gene expression	2	PPARA, PPARG
Transcriptional regulation of white adipocyte differentiation	2	PPARA, PPARG
SUMOylation of intracellular receptors	2	PPARA, PPARG
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	2	PPARA, PPARG
BMAL1:CLOCK,NPAS2 activates circadian expression	1	PPARA
Carnitine shuttle	1	PPARD
Transcriptional activation of mitochondrial biogenesis	1	PPARA
Activation of gene expression by SREBF (SREBP)	1	PPARA
Regulation of lipid metabolism by PPARalpha	1	PPARA
Signaling by Retinoic Acid	1	PPARD
Regulation of PTEN gene transcription	1	PPARG
MECP2 regulates transcription factors	1	PPARG
Cytoprotection by HMOX1	1	PPARA
Heme signaling	1	PPARA
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	PPARG
Expression of BMAL (ARNTL), CLOCK, and NPAS2	1	PPARA
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	1	PPARA

Dominant GO biological processes

GO term	Targets
negative regulation of transcription by RNA polymerase II	3
fatty acid metabolic process	3
heart development	3
hormone-mediated signaling pathway	3
negative regulation of cholesterol storage	3
cell differentiation	3
intracellular receptor signaling pathway	3
positive regulation of DNA-templated transcription	3
positive regulation of fatty acid metabolic process	3
positive regulation of transcription by RNA polymerase II	3
positive regulation of fatty acid oxidation	3
negative regulation of inflammatory response	3
negative regulation of miRNA transcription	3
regulation of DNA-templated transcription	3
response to nutrient	2

Indications & clinical

Indications

3 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
metabolic dysfunction-associated steatotic liver disease	3	MONDO:0013209	EFO:0003095
metabolic dysfunction-associated steatohepatitis	3	MONDO:0007027	EFO:1001249
diffuse scleroderma	2	MONDO:0005019	EFO:0000404

Clinical trials

Total trials: 7.

Phase distribution

Phase	Trials
PHASE2	4
PHASE1	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04849728	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )
NCT02503644	PHASE2	COMPLETED	Proof-of-concept Trial of IVA337 in Diffuse Cutaneous Systemic Sclerosis
NCT03008070	PHASE2	COMPLETED	Phase 2b Study in NASH to Assess IVA337
NCT03459079	PHASE2	COMPLETED	Lanifibranor in Patients With Type 2 Diabetes & Nonalcoholic Fatty Liver Disease
NCT05232071	PHASE2	COMPLETED	Placebo-controlled, Proof-of-concept Study to Evaluate the Safety and Efficacy of Lanifibranor Alone and in Combination With SGLT2 Inhibitor EmpaGliflozin in patiEnts With NASH and Type 2 Diabetes Mellitus
NCT03866369	PHASE1	COMPLETED	Multiple Ascending Dose Phase I Study in Order to Define Lanifibranor (IVA337) Supra-thjerapeutic Dose
NCT06126562	PHASE1	COMPLETED	A Pharmacokinetic Study of Lanifibranor in Healthy Adult Chinese Subjects

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

93 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
ELAFIBRANOR	ChEMBL	Phase 4 (approved)	PPARA, PPARD, PPARG
PEMAFIBRATE	ChEMBL	Phase 4 (approved)	PPARA, PPARD, PPARG
PIOGLITAZONE	ChEMBL	Phase 4 (approved)	PPARA, PPARD, PPARG
ROSIGLITAZONE	ChEMBL	Phase 4 (approved)	PPARA, PPARD, PPARG
ALEGLITAZAR	ChEMBL	Phase 3	PPARA, PPARD, PPARG
BEZAFIBRATE	ChEMBL	Phase 3	PPARA, PPARD, PPARG
GAMOLENIC ACID	ChEMBL	Phase 3	PPARA, PPARD, PPARG
ICOSAPENT	ChEMBL	Phase 3	PPARA, PPARD, PPARG
DIHOMO-GAMMA-LINOLENIC ACID	ChEMBL	Phase 2	PPARA, PPARD, PPARG
FARGLITAZAR	ChEMBL	Phase 2	PPARA, PPARD, PPARG
GW501516	ChEMBL	Phase 2	PPARA, PPARD, PPARG
GW590735	ChEMBL	Phase 2	PPARA, PPARD, PPARG
INDEGLITAZAR	ChEMBL	Phase 2	PPARA, PPARD, PPARG
LINOLEIC ACID	ChEMBL	Phase 2	PPARA, PPARD, PPARG
LY-518674	ChEMBL	Phase 2	PPARA, PPARD, PPARG
NAVEGLITAZAR	ChEMBL	Phase 2	PPARA, PPARD, PPARG
OLEIC ACID	ChEMBL	Phase 2	PPARA, PPARD, PPARG
PIRINIXIC ACID	ChEMBL	Phase 2	PPARA, PPARD, PPARG
SELADELPAR	ChEMBL + PubChem	Phase 4 (approved)	PPARA, PPARD
BERBERINE	ChEMBL	Phase 4 (approved)	PPARA, PPARD
FENOFIBRATE	ChEMBL	Phase 4 (approved)	PPARA, PPARG
FENOFIBRIC ACID	ChEMBL	Phase 4 (approved)	PPARA, PPARG
GEMFIBROZIL	ChEMBL	Phase 4 (approved)	PPARA, PPARG
IMIGLITAZAR	ChEMBL	Phase 3	PPARA, PPARG
LOBEGLITAZONE	ChEMBL	Phase 3	PPARA, PPARG
MURAGLITAZAR	ChEMBL	Phase 3	PPARA, PPARG
NAMODENOSON	ChEMBL	Phase 3	PPARD, PPARG
TESAGLITAZAR	ChEMBL	Phase 3	PPARA, PPARG
RAGAGLITAZAR	ChEMBL	Phase 2	PPARA, PPARG
REGLITAZAR	ChEMBL	Phase 2	PPARA, PPARG
FULVESTRANT	ChEMBL + PubChem	Phase 4 (approved)	PPARG
BENZBROMARONE	ChEMBL	Phase 4 (approved)	PPARG
BEXAROTENE	ChEMBL	Phase 4 (approved)	PPARG
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	PPARG
CANNABIDIOL	ChEMBL	Phase 4 (approved)	PPARG
CARVEDILOL	ChEMBL	Phase 4 (approved)	PPARG
CEFAMANDOLE	ChEMBL	Phase 4 (approved)	PPARG
CEFOTAXIME	ChEMBL	Phase 4 (approved)	PPARG
CEFOXITIN	ChEMBL	Phase 4 (approved)	PPARG
CEFTAZIDIME	ChEMBL	Phase 4 (approved)	PPARG
CEFTRIAXONE	ChEMBL	Phase 4 (approved)	PPARG
CIPROFIBRATE	ChEMBL	Phase 4 (approved)	PPARA
CLOBETASOL PROPIONATE	ChEMBL	Phase 4 (approved)	PPARG
CLOFIBRATE	ChEMBL	Phase 4 (approved)	PPARA
CYCLOSPORINE	ChEMBL	Phase 4 (approved)	PPARA
EFAVIRENZ	ChEMBL	Phase 4 (approved)	PPARG
GLYBURIDE	ChEMBL	Phase 4 (approved)	PPARG
INDOMETHACIN	ChEMBL	Phase 4 (approved)	PPARG
LASOFOXIFENE	ChEMBL	Phase 4 (approved)	PPARG
LEVOTHYROXINE	ChEMBL	Phase 4 (approved)	PPARG
LIOTHYRONINE	ChEMBL	Phase 4 (approved)	PPARG
LUMIRACOXIB	ChEMBL	Phase 4 (approved)	PPARG
MASOPROCOL	ChEMBL	Phase 4 (approved)	PPARG
METHYLENE BLUE	ChEMBL	Phase 4 (approved)	PPARG
MONTELUKAST	ChEMBL	Phase 4 (approved)	PPARG
NINTEDANIB	ChEMBL	Phase 4 (approved)	PPARG
RACECADOTRIL	ChEMBL	Phase 4 (approved)	PPARA
RIMONABANT	ChEMBL	Phase 4 (approved)	PPARG
SULINDAC	ChEMBL	Phase 4 (approved)	PPARG
TELMISARTAN	ChEMBL	Phase 4 (approved)	PPARG