Etrasimod

Summary

Etrasimod (CHEMBL3358920) is an approved small-molecule antibacterial agent (ATC L04AE05) targeting S1PR1, S1PR4, and S1PR5; indicated across 8 conditions including ulcerative colitis and crohn disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L04AE05
• Targets: 3 (S1PR1, S1PR4, S1PR5)
• Indications: 8 conditions
• Clinical trials: 26
• Chemistry: 457.5 Da · C26H26F3NO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3358920
Name	Etrasimod
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	44623998
ChEBI	CHEBI:229230
ATC	L04AE05
Molecular formula	C26H26F3NO3
Molecular weight	457.5
InChIKey	MVGWUTBTXDYMND-QGZVFWFLSA-N

SMILES: C1CCC(C1)C2=C(C=C(C=C2)COC3=CC4=C(C=C3)NC5=C4CC[C@@H]5CC(=O)O)C(F)(F)F

IUPAC name: 2-[(3R)-7-[[4-cyclopentyl-3-(trifluoromethyl)phenyl]methoxy]-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid

ChEBI definition: An organic heterotricyclic compound that is 1,2,3,4-tetrahydrocyclopenta[b]indole substituted by carboxymethyl and [4-cyclopentyl-3-(trifluoromethyl)phenyl]methoxy groups at positions 3R and 7, respectively. It is a potent and functional antagonist of the sphingosine-1-phosphate-1 (S1P1) receptor (IC50 = 1.88 nM in CHO cells).

Pharmacological roles (ChEBI): antibacterial agent, sphingosine-1-phosphate receptor 1 antagonist, immunosuppressive agent, anti-inflammatory drug.

Also known as: APD-334, APD-334(FREE ACID), Apd334, APD334, Etrasimod, ETRASIMOD

Parent form; salt/anhydrous children: CHEMBL3989933

Patent coverage: 281 distinct patent families (817 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 601 (74%) 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
S1PR1	S1P1 receptor	Agonist	9.24	0.2%	P21453
S1PR4	S1P4 receptor	Agonist	6.83	0.2%	O95977
S1PR5	S1P5 receptor	Agonist	7.61	0%	Q9H228

Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: Sphingosine 1-phosphate receptor 1, Sphingosine 1-phosphate receptor 1, Sphingosine 1-phosphate receptor 5, Adenosine receptor A3, Sphingosine 1-phosphate receptor 4, Sphingosine 1-phosphate receptor 1.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
S1PR1	10.4	EC50	0.04	nM	CHEMBL_ACT_14987117
S1PR1	9.99	EC50	0.1	nM	CHEMBL_ACT_28516256
P48303	9.49	EC50	0.32	nM	CHEMBL_ACT_14987090
O08530	9.36	EC50	0.44	nM	CHEMBL_ACT_14987092
S1PR1	8.73	IC50	1.88	nM	CHEMBL_ACT_14987093
S1PR1	8.21	EC50	6.1	nM	CHEMBL_ACT_14987084
S1PR1	8.2	EC50	6.31	nM	CHEMBL_ACT_25708622
S1PR5	7.61	EC50	24.4	nM	CHEMBL_ACT_14987060
S1PR4	6.83	EC50	147	nM	CHEMBL_ACT_14987062
ADORA3	5.48	IC50	3300	nM	CHEMBL_ACT_14985793

Target pathways

Aggregated over 3 target gene(s): S1PR1, S1PR4, S1PR5.

Top Reactome pathways

16 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	3	S1PR1, S1PR4, S1PR5
Signaling by GPCR	3	S1PR1, S1PR4, S1PR5
Class A/1 (Rhodopsin-like receptors)	3	S1PR1, S1PR4, S1PR5
Lysosphingolipid and LPA receptors	3	S1PR1, S1PR4, S1PR5
GPCR ligand binding	3	S1PR1, S1PR4, S1PR5
GPCR downstream signalling	2	S1PR4, S1PR5
G alpha (i) signalling events	2	S1PR4, S1PR5
Cytokine Signaling in Immune system	1	S1PR1
Disease	1	S1PR1
Immune System	1	S1PR1
Signaling by Interleukins	1	S1PR1
Infectious disease	1	S1PR1
Interleukin-4 and Interleukin-13 signaling	1	S1PR1
Potential therapeutics for SARS	1	S1PR1
SARS-CoV Infections	1	S1PR1
Viral Infection Pathways	1	S1PR1

Dominant GO biological processes

GO term	Targets
sphingosine-1-phosphate receptor signaling pathway	3
G protein-coupled receptor signaling pathway	3
adenylate cyclase-activating G protein-coupled receptor signaling pathway	3
signal transduction	3
angiogenesis	1
blood vessel maturation	1
cardiac muscle tissue growth involved in heart morphogenesis	1
chemotaxis	1
cell adhesion	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
brain development	1
cell population proliferation	1
cell migration	1
transmission of nerve impulse	1

Indications & clinical

Indications

8 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
ulcerative colitis	3	MONDO:0005101	EFO:0000729
Crohn disease	3	MONDO:0005011	EFO:0000384
inflammatory bowel disease	2	MONDO:0005265	EFO:0003767
primary biliary cholangitis	2	MONDO:0005388	EFO:1001486
pyoderma	2	MONDO:0002922	HP:0000999
atopic eczema	2	MONDO:0004980	EFO:0000274
alopecia areata	2	MONDO:0005340	EFO:0004192
eosinophilic esophagitis	2	MONDO:0005361	EFO:0004232

Clinical trials

Total trials: 26.

Phase distribution

Phase	Trials
PHASE2	14
PHASE3	6
Not specified	4
PHASE2/PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03950232	PHASE3	ACTIVE_NOT_RECRUITING	An Extension Study for Treatment of Moderately to Severely Active Ulcerative Colitis
NCT03945188	PHASE3	COMPLETED	Etrasimod Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis
NCT03996369	PHASE3	COMPLETED	Etrasimod Versus Placebo as Induction Therapy in Moderately to Severely Active Ulcerative Colitis
NCT04173273	PHASE3	TERMINATED	A Study Evaluating the Efficacy and Safety of Oral Etrasimod in the Treatment of Adult Participants With Moderately to Severely Active Crohn’s Disease
NCT04176588	PHASE3	UNKNOWN	A Phase 3 Study of Etrasimod in Subjects With Moderately to Severely Active Ulcerative Colitis
NCT04706793	PHASE3	COMPLETED	Oral Etrasimod Versus Placebo for the Treatment of Moderately to Severely Active Ulcerative Colitis in Adult Japanese Participants (ELEVATE UC 40 JAPAN)
NCT05732454	PHASE2/PHASE3	TERMINATED	A Study to Learn About the Study Medicine Etrasimod in Adults With Moderate to Severe Atopic Dermatitis (AD) Who Have Already Tried Treatments Taken by Mouth or by Injection
NCT05287126	PHASE2	RECRUITING	A Study to Evaluate Etrasimod Treatment in Adolescents With Ulcerative Colitis
NCT07470879	PHASE2	RECRUITING	A Study of How the Medicine Called Etrasimod Works in Children With the Gut Disease Called Ulcerative Colitis
NCT07486921	PHASE2	NOT_YET_RECRUITING	Etrasimod as Prevention of Pouchitis
NCT02447302	PHASE2	COMPLETED	Safety and Efficacy of Etrasimod (APD334) in Patients With Ulcerative Colitis
NCT02536404	PHASE2	COMPLETED	Extension Study of APD334-003 in Patients With Moderately to Severely Active Ulcerative Colitis
NCT03072953	PHASE2	TERMINATED	Efficacy and Safety of APD334 in Patients With Pyoderma Gangrenosum
NCT03139032	PHASE2	TERMINATED	Efficacy and Safety of Etrasimod (APD334) in Inflammatory Bowel Disease Patients With Active Skin Extra-intestinal Manifestations
NCT03155932	PHASE2	TERMINATED	Safety, Tolerability, and Efficacy of Etrasimod (APD334) in Participants With Primary Biliary Cholangitis
NCT04162769	PHASE2	COMPLETED	A Study to Assess the Safety and Efficacy of Etrasimod in Subjects With Moderate-to-Severe Atopic Dermatitis
NCT04556734	PHASE2	COMPLETED	Safety and Efficacy of Oral Etrasimod in Adult Participants With Moderate-to-Severe Alopecia Areata
NCT04607837	PHASE2	COMPLETED	Etrasimod Versus Placebo for the Treatment of Moderately Active Ulcerative Colitis
NCT04682639	PHASE2	COMPLETED	A Study to Assess the Safety and Efficacy of Oral Etrasimod in Adult Participants With Eosinophilic Esophagitis
NCT05061446	PHASE2	COMPLETED	Etrasimod Dose-Ranging Versus Placebo as Induction Therapy Study in Adult Japanese Subjects With Moderately to Severely Active Ulcerative Colitis
NCT06521762	PHASE2	WITHDRAWN	Etrasimod for Immune Checkpoint Inhibitor Diarrhea and Colitis
NCT07153159	PHASE1	RECRUITING	A Study to Learn How the Study Medicine Called Etrasimod is Taken up Into Blood and Breastmilk of Healthy Breastfeeding Women
NCT06025227	Not specified	AVAILABLE	Provide Pre-approval Single Patient Expanded Access (Compassionate Use) of Etrasimod for Patients.
NCT06294925	Not specified	RECRUITING	A Study to Learn About the Effectiveness of Etrasimod in People With Ulcerative Colitis
NCT06398626	Not specified	RECRUITING	An Observational Study of Etrasimod in Adult Patients With Moderate to Severe Ulcerative Colitis
NCT07243639	Not specified	RECRUITING	Efficacy and Safety of Etrasimod in Elderly Patients With Ulcerative Colitis

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

9 molecules share ≥1 primary target. Top 9 by shared-target count:

Molecule	Source	Status	Shared targets
FINGOLIMOD	ChEMBL + PubChem	Phase 4 (approved)	S1PR1, S1PR4, S1PR5
OZANIMOD	ChEMBL + PubChem	Phase 4 (approved)	S1PR1, S1PR4, S1PR5
SIPONIMOD	ChEMBL + PubChem	Phase 4 (approved)	S1PR1, S1PR4, S1PR5
PONESIMOD	ChEMBL	Phase 4 (approved)	S1PR1
CENERIMOD	ChEMBL	Phase 3	S1PR1
AMISELIMOD	ChEMBL	Phase 2	S1PR1
ICANBELIMOD	ChEMBL	Phase 2	S1PR1
NIGULDIPINE	ChEMBL	Phase 2	S1PR1
PINAFIDE	ChEMBL	Phase 2	S1PR1