Lifitegrast

Identification

Summary

Lifitegrast is a medication used to treat dry eye disease.

Brand Names

Xiidra

Generic Name

Lifitegrast

DrugBank Accession Number

DB11611

Background

Lifitegrast is a FDA approved drug for the treatment of keratoconjunctivitis sicca (dry eye syndrome). It is a tetrahydroisoquinoline derivative and lymphocyte function-associated antigen-1 ( LFA-1) antagonist that was discovered through the rational design process. The ophthalmic solution was approved in July, 2016 under the trade name Xiidra. It has shown to protect the corneal surface and alleviate the symptoms of dry eye syndrome with fast onset of action and well tolerated profile in both local and systemic setting ².

Type

Small Molecule

Groups

Approved

Structure

3D

Download

MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Lifitegrast (DB11611)

×

Close

Weight

Average: 615.48
Monoisotopic: 614.0681277

Chemical Formula

C₂₉H₂₄Cl₂N₂O₇S

Synonyms

• Lifitegrast

External IDs

• SAR 1118
• SAR-1118
• SHP-606
• SHP606

Poor quality drug data slowing you down?

Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.

Download eBook

Poor quality drug data slowing you down?

Download eBook

Pharmacology

Indication

For the treatment of signs and symptoms of keratoconjunctivitis sicca (dry eye syndrome).

Reduce drug development failure rates

Build, train, & validate machine-learning models
with evidence-based and structured datasets.

See how

Build, train, & validate predictive machine-learning models with structured datasets.

See how

Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Symptomatic treatment of	Dry eye disease		••••••••••••			••••••••••

Create Account

Contraindications & Blackbox Warnings

Prevent Adverse Drug Events Today

Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.

Learn more

Avoid life-threatening adverse drug events with our Clinical API

Learn more

Pharmacodynamics

Lifitegrast addresses both the symptoms and the resulting ocular surface damage by interfering with ocular inflammatory cycle ². Lifitegrast is a lymphocyte function–associated antigen-1 antagonist through direct competitive antagonism and sequentially inhibits the T-cell recruitment, activation, and proinflammatory cytokine release associated with dry eye syndrome ⁴.

Mechanism of action

Lifitegrast binds to the integrin lymphocyte function-associated antigen-1 (LFA-1), a cell surface protein found on leukocytes and blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1 (ICAM-1). ICAM-1 may be overexpressed in corneal and conjunctival tissues in dry eye disease. LFA-1/ICAM-1 interaction can contribute to the formation of an immunological synapse resulting in T-cell proliferation/activation and migration to target tissues. In vitro studies demonstrated that lifitegrast may inhibit T-cell adhesion to ICAM-1 in a human T-cell line and may inhibit secretion of inflammatory cytokines, inflammatory mediators, chemokines, TNF-α, and IL-1 in human peripheral blood mononuclear cells.

Target	Actions	Organism
AIntegrin alpha-L	antagonist	Humans

Absorption

The mean peak plasma concentration (Cmax) of 1.70ng/mL was reached within 15 minutes of application. Quantifiable trough plasma concentrations ranged from 0.55 ng/mL to 3.74 ng/mL ⁶. Observations show limited systemic exposure that produces significant clinical outcomes.

Volume of distribution

Not Available

Protein binding

Human plasma protein binding of lifitegrast was approximately 99%, independent of concentration (50 to 1000ng/mL). Binding to isolated human serum albumin was 95% to 98%, and 31.6% to 51.1% to human α1-acid glycoprotein ⁶.

Metabolism

Based on the findings of an in vitro metabolism study using fresh human hepatocytes, lifitegrast does not appear to undergo significant metabolism ⁶.

Route of elimination

Not possible to perform mass balance study to determine the main route of elimination ⁶.

Half-life

Not possible to calculate plasma elimination half-life based on plasma concentrations of lifitegrast, but reported to be relatively short in rat I.V. pharmacokinetics study ⁵.

Clearance

Not possible to calculate clearance rate based on plasma concentrations of lifitegrast, but reported to be relatively fast in rat I.V. pharmacokinetics study ⁵. It is predicted that lifitegrast is cleared via nasal and subsequently gastrointestinal tract ⁶.

Adverse Effects

Improve decision support & research outcomes

With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!

See the data

Improve decision support & research outcomes with our structured adverse effects data.

See a data sample

Toxicity

Some adverse effects in 5-25% of the patients include instillation site irritation, dysgeusia and reduced visual acuity. There is no evidence or reports of potential carcinogenic, mutagenic or fertility-altering effects of this drug.

Pathways

Not Available

Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Not Available

Food Interactions

No interactions found.

Products

Drug product information from 10+ global regions

Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.

Access now

Access drug product information from over 10 global regions.

Access now

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Lifitegrast sodium	QG18FLP1KP	1119276-80-0	BPWOKOSRORLLIN-BQAIUKQQSA-M

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Xiidra	Solution	5 % w/v	Ophthalmic	Novartis	2018-02-12	Not applicable
Xiidra	Solution / drops	50 mg/1mL	Ophthalmic	Novartis Pharmaceuticals Corporation	2016-07-11	Not applicable
Xiidra	Solution / drops	50 mg/1mL	Ophthalmic	Bausch & Lomb Incorporated	2024-01-02	Not applicable
Xiidra	Solution / drops	50 mg/1mL	Ophthalmic	Takeda Pharmaceuticals America, Inc.	2016-07-11	2023-03-31

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Lifitegrast	For solution	50 mg/1mL	Ophthalmic	Aurobindo Pharma Limited	2023-11-07	Not applicable

Categories

ATC Codes

S01XA25 — Lifitegrast

• S01XA — Other ophthalmologicals
• S01X — OTHER OPHTHALMOLOGICALS
• S01 — OPHTHALMOLOGICALS
• S — SENSORY ORGANS

Drug Categories

• Amino Acids
• Amino Acids, Aromatic
• Amino Acids, Cyclic
• Amino Acids, Peptides, and Proteins
• Anti-Inflammatory Agents
• Anti-inflammatory Agents, Miscellaneous
• Compounds used in a research, industrial, or household setting
• Cytochrome P-450 CYP2C9 Inhibitors
• Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
• Cytochrome P-450 Enzyme Inhibitors
• Lymphocyte Function-Associated Antigen-1
• Lymphocyte Function-Associated Antigen-1 Antagonist
• Lymphocyte Function-Associated Antigen-1 Antagonists
• OATP2B1/SLCO2B1 substrates
• Ophthalmic Solutions
• Ophthalmologicals
• Pharmaceutical Preparations
• Pharmaceutical Solutions
• Sensory Organs
• Solutions
• Sulfur Compounds

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Phenylalanine and derivatives

Alternative Parents

N-acyl-alpha amino acids / Phenylpropanoic acids / Tetrahydroisoquinolines / 2-halobenzoic acids and derivatives / Amphetamines and derivatives / Benzenesulfonyl compounds / Benzofurans / Aryl chlorides / Vinylogous halides / Tertiary carboxylic acid amides / Sulfones / Furans / Heteroaromatic compounds / Secondary carboxylic acid amides / Oxacyclic compounds / Azacyclic compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Organochlorides / Carbonyl compounds / Organonitrogen compounds / Hydrocarbon derivatives

show 13 more

Substituents

2-halobenzoic acid or derivatives / 3-phenylpropanoic-acid / Amphetamine or derivatives / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenesulfonyl group / Benzenoid / Benzofuran / Carbonyl group / Carboxamide group / Carboxylic acid / Furan / Halobenzoic acid or derivatives / Heteroaromatic compound / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Monocyclic benzene moiety / N-acyl-alpha amino acid or derivatives / N-acyl-alpha-amino acid / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organochloride / Organohalogen compound / Organoheterocyclic compound / Organonitrogen compound / Organooxygen compound / Organosulfur compound / Oxacycle / Phenylalanine or derivatives / Secondary carboxylic acid amide / Sulfone / Sulfonyl / Tertiary carboxylic acid amide / Tetrahydroisoquinoline / Vinylogous halide

show 28 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Affected organisms

Not Available

Chemical Identifiers

UNII

038E5L962W

CAS number

1025967-78-5

InChI Key

JFOZKMSJYSPYLN-QHCPKHFHSA-N

InChI

InChI=1S/C29H24Cl2N2O7S/c1-41(38,39)20-4-2-3-16(11-20)12-23(29(36)37)32-27(34)25-22(30)13-19-15-33(9-7-21(19)26(25)31)28(35)18-6-5-17-8-10-40-24(17)14-18/h2-6,8,10-11,13-14,23H,7,9,12,15H2,1H3,(H,32,34)(H,36,37)/t23-/m0/s1

IUPAC Name

(2S)-2-{[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinolin-6-yl]formamido}-3-(3-methanesulfonylphenyl)propanoic acid

SMILES

CS(=O)(=O)C1=CC(C[C@H](NC(=O)C2=C(Cl)C3=C(CN(CC3)C(=O)C3=CC=C4C=COC4=C3)C=C2Cl)C(O)=O)=CC=C1

References

General References

1. Tauber J, Karpecki P, Latkany R, Luchs J, Martel J, Sall K, Raychaudhuri A, Smith V, Semba CP: Lifitegrast Ophthalmic Solution 5.0% versus Placebo for Treatment of Dry Eye Disease: Results of the Randomized Phase III OPUS-2 Study. Ophthalmology. 2015 Dec;122(12):2423-31. doi: 10.1016/j.ophtha.2015.08.001. Epub 2015 Sep 11. [Article]
2. Abidi A, Shukla P, Ahmad A: Lifitegrast: A novel drug for treatment of dry eye disease. J Pharmacol Pharmacother. 2016 Oct-Dec;7(4):194-198. doi: 10.4103/0976-500X.195920. [Article]
3. Paton DM: Lifitegrast: First LFA-1/ICAM-1 antagonist for treatment of dry eye disease. Drugs Today (Barc). 2016 Sep;52(9):485-493. [Article]
4. Holland EJ, Luchs J, Karpecki PM, Nichols KK, Jackson MA, Sall K, Tauber J, Roy M, Raychaudhuri A, Shojaei A: Lifitegrast for the Treatment of Dry Eye Disease: Results of a Phase III, Randomized, Double-Masked, Placebo-Controlled Trial (OPUS-3). Ophthalmology. 2017 Jan;124(1):53-60. doi: 10.1016/j.ophtha.2016.09.025. Epub 2016 Oct 27. [Article]
5. Zhong M, Gadek TR, Bui M, Shen W, Burnier J, Barr KJ, Hanan EJ, Oslob JD, Yu CH, Zhu J, Arkin MR, Evanchik MJ, Flanagan WM, Hoch U, Hyde J, Prabhu S, Silverman JA, Wright J: Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye. ACS Med Chem Lett. 2012 Jan 31;3(3):203-6. doi: 10.1021/ml2002482. eCollection 2012 Mar 8. [Article]
6. FDA Clinical Pharmacology and Biopharmaceutics Review [Link]
7. FDA Approved Drug Products: Xiidra (lifitegrast) ophthalmic solution [Link]

External Links

KEGG Drug

D10374

PubChem Compound

11965427

PubChem Substance

347828006

ChemSpider

10139520

BindingDB

50386331

RxNav

1801820

ChEBI

133023

ChEMBL

CHEMBL2048028

ZINC

ZINC000084668739

Drugs.com

Drugs.com Drug Page

Wikipedia

Lifitegrast

FDA label

Download (1.22 MB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Completed	Supportive Care	Contact Lens Discomfort (CLD) / Contact Lens Related Dry Eye / Contact Lenses	1
4	Completed	Treatment	Dry Eye Syndrome (DES)	1
4	Completed	Treatment	Dry Eyes	3
4	Recruiting	Treatment	Corneal Diseases	1
4	Recruiting	Treatment	Dry Eyes	2

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
For solution	Ophthalmic	50 mg/1mL
Solution	Ophthalmic	5 % w/v
Solution	Ophthalmic	50.00 mg
Solution / drops	Ophthalmic	50 mg/1mL

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US8927574	No	2015-01-06	2030-11-12
US7928122	No	2011-04-19	2024-11-05
US9085553	No	2015-07-21	2033-07-25
US9353088	No	2016-05-31	2030-10-21
US9216174	No	2015-12-22	2024-11-05
US7314938	No	2008-01-01	2025-03-10
US8084047	No	2011-12-27	2026-05-17
US8367701	No	2013-02-05	2029-04-15
US8168655	No	2012-05-01	2029-05-09
US8592450	No	2013-11-26	2026-05-17
US7790743	No	2010-09-07	2024-11-05
US7745460	No	2010-06-29	2024-11-05
US9447077	No	2016-09-20	2029-04-15
US9890141	No	2018-02-13	2030-10-21
US10124000	No	2018-11-13	2024-11-05
US11058677	No	2021-07-13	2033-12-18

Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	Soluble	FDA Label

Predicted Properties

Property	Value	Source
Water Solubility	0.00571 mg/mL	ALOGPS
logP	3.96	ALOGPS
logP	4.02	Chemaxon
logS	-5	ALOGPS
pKa (Strongest Acidic)	3.27	Chemaxon
pKa (Strongest Basic)	-1.3	Chemaxon
Physiological Charge	-1	Chemaxon
Hydrogen Acceptor Count	6	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	133.99 Å2	Chemaxon
Rotatable Bond Count	7	Chemaxon
Refractivity	154.48 m3·mol-1	Chemaxon
Polarizability	59.49 Å3	Chemaxon
Number of Rings	5	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	Yes	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-014i-0160079000-8f35a0a456f384c2d9a6
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03xr-1029027000-ac5e3cb3f8945f90e610
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-016s-0580392000-3f9f0d666b9465909f2b
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-001i-9110111000-bf1d08c396f1b2600110
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-00kb-0911421000-76d15dfd9d9d79083767
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-001i-9501021000-e6ec0106b23178a8c8e3

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å2)	Source type	Source
[M-H]-	228.20387	predicted	DeepCCS 1.0 (2019)
[M+H]+	230.36162	predicted	DeepCCS 1.0 (2019)
[M+Na]+	236.23138	predicted	DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models

Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.

Learn more

Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.

Learn more

Details1. Integrin alpha-L

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Antagonist

General Function

Metal ion binding

Specific Function

Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated ...

Gene Name

ITGAL

Uniprot ID

P20701

Uniprot Name

Integrin alpha-L

Molecular Weight

128768.495 Da

References

1. Paton DM: Lifitegrast: First LFA-1/ICAM-1 antagonist for treatment of dry eye disease. Drugs Today (Barc). 2016 Sep;52(9):485-493. [Article]

×

Identify potential medication risks

Easily compare up to 40 drugs with our drug interaction checker.

Get severity rating, description, and management advice.

Learn more

Drug created at July 13, 2016 15:57 / Updated at February 20, 2024 23:55