Selonsertib

Summary

Selonsertib (CHEMBL3916717) is a phase-3 clinical-stage small molecule targeting MAP3K5; indicated across 5 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: 1 (MAP3K5)
• Indications: 5 conditions
• Clinical trials: 5
• Chemistry: 445.5 Da · C24H24FN7O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3916717
Name	Selonsertib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	71245288
Molecular formula	C24H24FN7O
Molecular weight	445.5
InChIKey	YIDDLAAKOYYGJG-UHFFFAOYSA-N

SMILES: CC1=CC(=C(C=C1N2C=C(N=C2)C3CC3)C(=O)NC4=CC=CC(=N4)C5=NN=CN5C(C)C)F

IUPAC name: 5-(4-cyclopropylimidazol-1-yl)-2-fluoro-4-methyl-N-[6-(4-propan-2-yl-1,2,4-triazol-3-yl)-2-pyridinyl]benzamide

Also known as: Gs-4997, GS-4997, Selonsertib, SELONSERTIB, selonsertib, SELONSERTIB HYDROCHLORIDE

Parent form; salt/anhydrous children: CHEMBL5559017, CHEMBL5559907, CHEMBL5562336, CHEMBL5565908

Patent coverage: 462 distinct patent families (1,422 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,412 (99%) 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
MAP3K5	mitogen-activated protein kinase kinase kinase 5	Inhibition	8.49	0.4%	Q99683

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Mitogen-activated protein kinase kinase kinase 6, Mitogen-activated protein kinase kinase kinase 5.

Bioactivity

ChEMBL activities: 207 potent at pChembl ≥ 5 of 207 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
MAP3K5	8.7	EC50	2	nM	CHEMBL_ACT_22883486
MAP3K5	8.7	EC50	2	nM	CHEMBL_ACT_25871685
MAP3K5	8.52	IC50	3	nM	CHEMBL_ACT_22883439
MAP3K5	8.52	IC50	3	nM	CHEMBL_ACT_25754667
MAP3K5	8.52	IC50	3	nM	CHEMBL_ACT_25754668
MAP3K5	8.52	IC50	3	nM	CHEMBL_ACT_25871682
MAP3K5	8.4	IC50	4	nM	CHEMBL_ACT_25754666
MAP3K5	8.3	IC50	5.01	nM	CHEMBL_ACT_16857956
MAP3K5	8.3	IC50	5	nM	CHEMBL_ACT_18048935
MAP3K5	8.3	IC50	5	nM	CHEMBL_ACT_22479279
MAP3K5	8.3	IC50	5	nM	CHEMBL_ACT_25871650
MAP3K5	8.26	IC50	5.5	nM	CHEMBL_ACT_20608780
MAP3K5	8.26	IC50	5.5	nM	CHEMBL_ACT_25755822
MAP3K5	8.23	IC50	5.9	nM	CHEMBL_ACT_18924238
MAP3K5	8.23	IC50	5.9	nM	CHEMBL_ACT_23197540
MAP3K5	8.22	IC50	6	nM	CHEMBL_ACT_18479963
MAP3K5	7.96	IC50	11	nM	CHEMBL_ACT_25754795
MAP3K5	7.89	IC50	12.9	nM	CHEMBL_ACT_23283915
MAP3K5	7.85	IC50	14	nM	CHEMBL_ACT_25754797
MAP3K5	7.8	IC50	16	nM	CHEMBL_ACT_25754796
MAP3K5	7.77	IC50	17	nM	CHEMBL_ACT_25554038
MAP3K5	7.75	IC50	18	nM	CHEMBL_ACT_25754751
MAP3K5	7.7	IC50	20	nM	CHEMBL_ACT_18924264
MAP3K5	7.7	IC50	20	nM	CHEMBL_ACT_20608788
MAP3K5	7.7	IC50	20	nM	CHEMBL_ACT_25755672
MAP3K5	7.68	IC50	21	nM	CHEMBL_ACT_25754703
MAP3K5	7.68	IC50	21	nM	CHEMBL_ACT_25754750
MAP3K5	7.64	IC50	23	nM	CHEMBL_ACT_25754685
MAP3K5	7.64	IC50	23	nM	CHEMBL_ACT_25754704
MAP3K5	7.61	IC50	24.4	nM	CHEMBL_ACT_22479110

Target pathways

Aggregated over 1 target gene(s): MAP3K5.

Top Reactome pathways

4 total, by targets touching each:

Pathway	Targets	Genes
Cellular responses to stress	1	MAP3K5
Oxidative Stress Induced Senescence	1	MAP3K5
Cellular Senescence	1	MAP3K5
Cellular responses to stimuli	1	MAP3K5

Dominant GO biological processes

GO term	Targets
MAPK cascade	1
response to ischemia	1
JNK cascade	1
intrinsic apoptotic signaling pathway in response to oxidative stress	1
positive regulation of cardiac muscle cell apoptotic process	1
cellular response to amino acid starvation	1
response to endoplasmic reticulum stress	1
neuron intrinsic apoptotic signaling pathway in response to oxidative stress	1
p38MAPK cascade	1
positive regulation of apoptotic process	1
innate immune response	1
positive regulation of myoblast differentiation	1
positive regulation of DNA-templated transcription	1
positive regulation of JNK cascade	1
neuron apoptotic process	1

Indications & clinical

Indications

5 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
diabetic kidney disease	2	MONDO:0005016	EFO:0000401
pulmonary arterial hypertension	2	MONDO:0015924	EFO:0001361
alcoholic hepatitis	2	MONDO:0001505	EFO:1001345

Clinical trials

Total trials: 5.

Phase distribution

Phase	Trials
PHASE2	3
PHASE1	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02177786	PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Selonsertib (GS-4997) in Participants With Diabetic Kidney Disease
NCT02234141	PHASE2	COMPLETED	Selonsertib in Adults With Pulmonary Arterial Hypertension
NCT02854631	PHASE2	COMPLETED	Selonsertib in Combination With Prednisolone Versus Prednisolone Alone in Participants With Severe Alcoholic Hepatitis (AH)
NCT02509624	PHASE1	COMPLETED	Study to Evaluate the Pharmacokinetics of Selonsertib in Participants With Normal and Impaired Hepatic Function
NCT03087968	EARLY_PHASE1	WITHDRAWN	Evaluation of HepQuant SHUNT to Assess Liver Disease; Substudy Within GS-US-416-2124

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.

16 molecules share ≥1 primary target. Top 16 by shared-target count:

Molecule	Source	Status	Shared targets
LESTAURTINIB	ChEMBL	Phase 3	MAP3K5
AT-9283	ChEMBL	Phase 2	MAP3K5
Afatinib	PubChem	Approved	MAP3K5
Binimetinib	PubChem	Approved	MAP3K5
Cobimetinib	PubChem	Approved	MAP3K5
Crizotinib	PubChem	Approved	MAP3K5
dacomitinib	PubChem	Approved	MAP3K5
Fedratinib	PubChem	Approved	MAP3K5
Fostamatinib	PubChem	Approved	MAP3K5
Gefitinib	PubChem	Approved	MAP3K5
Idelalisib	PubChem	Approved	MAP3K5
Imatinib	PubChem	Approved	MAP3K5
Pazopanib	PubChem	Approved	MAP3K5
regorafenib	PubChem	Approved	MAP3K5
Selumetinib	PubChem	Approved	MAP3K5
Trametinib	PubChem	Approved	MAP3K5