Lifitegrast

Summary

Lifitegrast (CHEMBL2048028) is an approved small-molecule anti-inflammatory drug (ATC S01XA25) targeting ITGAL; indicated across 4 conditions including dry eye syndrome and eye disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: S01XA25
• Targets: 1 (ITGAL)
• Indications: 4 conditions
• Clinical trials: 27
• Chemistry: 615.5 Da · C29H24Cl2N2O7S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2048028
Name	Lifitegrast
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	11965427
ChEBI	CHEBI:133023
ATC	S01XA25
Molecular formula	C29H24Cl2N2O7S
Molecular weight	615.5
InChIKey	JFOZKMSJYSPYLN-QHCPKHFHSA-N

SMILES: CS(=O)(=O)C1=CC=CC(=C1)C[C@@H](C(=O)O)NC(=O)C2=C(C=C3CN(CCC3=C2Cl)C(=O)C4=CC5=C(C=C4)C=CO5)Cl

IUPAC name: (2S)-2-[[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(3-methylsulfonylphenyl)propanoic acid

ChEBI definition: An N-acyl-L-α-amino acid obtained by formal condensation of the carboxy group of N-[2-(1-benzofuran-6-carbonyl)]-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid with the amino group of 3-(methanesulfonyl)-L-phenylalanine. Used for treatment of keratoconjunctivitis sicca (dry eye syndrome).

Pharmacological roles (ChEBI): anti-inflammatory drug, lymphocyte function-associated antigen-1 antagonist.

Also known as: Lifitegrast, SAR 1118, SAR-1118, SHP-606, SHP606, Xiidra, LIFITEGRAST

Parent form; salt/anhydrous children: CHEMBL2048409, CHEMBL2048410

Patent coverage: 467 distinct patent families (1,078 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 885 (82%) 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
ITGAL	integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide)	Inhibition		0.2%	P20701

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Intercellular adhesion molecule (ICAM-1), Integrin alpha-L/beta-2, Intercellular adhesion molecule 1, Cytochrome P450 2C9.

Bioactivity

ChEMBL activities: 4 potent at pChembl ≥ 5 of 4 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ICAM1	8.53	IC50	2.98	nM	CHEMBL_ACT_10939112
ITGB2	8.05	IC50	9	nM	CHEMBL_ACT_10939035
ITGB2	7.13	IC50	74	nM	CHEMBL_ACT_10939056
CYP2C9	5.52	IC50	3000	nM	CHEMBL_ACT_10939115

Target pathways

Aggregated over 1 target gene(s): ITGAL.

Top Reactome pathways

14 total, by targets touching each:

Pathway	Targets	Genes
Hemostasis	1	ITGAL
Adaptive Immune System	1	ITGAL
Extracellular matrix organization	1	ITGAL
Innate Immune System	1	ITGAL
Immune System	1	ITGAL
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	ITGAL
Cell surface interactions at the vascular wall	1	ITGAL
Generic Transcription Pathway	1	ITGAL
Integrin cell surface interactions	1	ITGAL
Neutrophil degranulation	1	ITGAL
RNA Polymerase II Transcription	1	ITGAL
Gene expression (Transcription)	1	ITGAL
Transcriptional regulation by RUNX3	1	ITGAL
RUNX3 Regulates Immune Response and Cell Migration	1	ITGAL

Dominant GO biological processes

GO term	Targets
T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell	1
phagocytosis	1
inflammatory response	1
cell adhesion	1
heterophilic cell-cell adhesion	1
leukocyte cell-cell adhesion	1
cell-matrix adhesion	1
signal transduction	1
integrin-mediated signaling pathway	1
memory T cell extravasation	1
receptor clustering	1
cell-cell adhesion	1
T cell activation	1

Indications & clinical

Indications

2 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
dry eye syndrome	4	MONDO:0006733	EFO:1000906
eye disorder	4	MONDO:0005328	EFO:0003966

1 disease in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
atopic conjunctivitis	2	MONDO:0005642	EFO:0007141

Clinical trials

Total trials: 27.

Phase distribution

Phase	Trials
PHASE4	13
PHASE3	5
PHASE2	4
Not specified	2
PHASE1/PHASE2	1
EARLY_PHASE1	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03408015	PHASE4	WITHDRAWN	Effects of Xiidra on Closed Eye Tear Film Leukocytes in Dry Eye Disease
NCT03431272	PHASE4	WITHDRAWN	Use of 5.0% Lifitegrast Ophthalmic Solution for the Treatment of Dry Eye Disease in Contact Lens Wearers
NCT03451396	PHASE4	COMPLETED	Effect of Lifitegrast on Dry Eye Disease Signs and Symptoms
NCT03686878	PHASE4	COMPLETED	Lifitegrast 5% Ophthalmic Solution and Contact Lens Dryness
NCT03952481	PHASE4	WITHDRAWN	Effect of Lifitegrast 5% on Tear Film Markers
NCT04120987	PHASE4	WITHDRAWN	Ocular Inflammation in Cataract Patients and Response to Treatment With Xiidra
NCT04172961	PHASE4	UNKNOWN	Clinical Efficacy of Two Topical Dry Eye Drops for Central Corneal Stain Clearing Over 90 Days
NCT04297618	PHASE4	COMPLETED	The Effect of Xiidra on Comfort and Dryness in Symptomatic Contact Lens Wearers
NCT04413253	PHASE4	TERMINATED	Xiidra vs. Xiidra + Dextenza Treatment for Dry Eye Disease
NCT04669561	PHASE4	COMPLETED	The Chronology of Lifitegrast Effect on Anterior Surface Rehabilitation (CLEAR) Study
NCT05045053	PHASE4	UNKNOWN	Efficacy of Xiidra in Dry Eye Disease After Collagen Cross Linking
NCT05505292	PHASE4	COMPLETED	Lifitegrast 5% for the Treatment of Dry Eye In Habitual Soft Contact Lens Wearers
NCT05594745	PHASE4	COMPLETED	Treatment Regimens in Meibomian Gland Dysfunction
NCT01421498	PHASE3	COMPLETED	Safety and Efficacy Study of SAR 1118 to Treat Dry Eye Conducted in a Controlled Adverse Environment (CAE) (OPUS-1)
NCT01636206	PHASE3	COMPLETED	Safety Study of Lifitegrast to Treat Dry Eye
NCT01743729	PHASE3	COMPLETED	A Phase 3 Study to Evaluate the Efficacy of Lifitegrast in Subjects With Dry Eye
NCT02284516	PHASE3	COMPLETED	A Study to Evaluate Efficacy and Safety of Lifitegrast in Subjects With Dry Eye (OPUS-3)
NCT07111013	PHASE3	WITHDRAWN	A Study to Assess the Long-Term Safety of Lifitegrast/Perfluorohexyloctane Fixed-Dose Combination in Subjects With Dry Eye Disease
NCT07128628	PHASE2	RECRUITING	A Study Evaluating the Safety and Efficacy of a Fixed-Dose Combination for Dry Eye Disease
NCT00882687	PHASE2	COMPLETED	Efficacy Study to Evaluate the Effectiveness of 3 Concentrations of SAR 1118 in Allergic Conjunctivitis
NCT00926185	PHASE2	COMPLETED	A Study Evaluating the Efficacy of SAR 1118 (0.1%, 1.0%, 5.0%) Ophthalmic Solution in Subjects With Dry Eye Conducted in a Controlled Adverse Environment (CAE)
NCT04030962	PHASE1/PHASE2	COMPLETED	A Study of the Drugs AGN-242428 and AGN-231868 in Participants With Dry Eye Disease
NCT04734197	PHASE2	COMPLETED	A Research Study To See How Well an Eye Drop, SURF-100 (A Mycophenolic Acid/Betamethasone Sodium Phosphate Combination), Works and What Side Effects There Are in Subjects With Dry Eye Disease
NCT07040826	PHASE1	COMPLETED	Lifitegrast Eye Drops in Healthy Subjects：Phase I Study
NCT04792580	EARLY_PHASE1	COMPLETED	The Effects and Safety of 5% Lifitegrast Ophthalmic Solution in Subjects With Dry Eye Disease in Ocular Graft-versus-Host Disease
NCT03866629	Not specified	COMPLETED	The Effect Of Lifitegrast On Refractive Accuracy And Symptoms In Dry Eye Patients Undergoing Cataract Surgery
NCT05857748	Not specified	WITHDRAWN	Examining the Clinical Characteristics, Treatment Patterns, Real-world Effectiveness, and Healthcare Resource Utilization of Patients With Dry Eye Disease

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.

3 molecules share ≥1 primary target. Top 3 by shared-target count:

Molecule	Source	Status	Shared targets
LOVASTATIN	ChEMBL + PubChem	Phase 4 (approved)	ITGAL
Dexamethasone	PubChem	Approved	ITGAL
Tirofiban	PubChem	Approved	ITGAL