Lifitegrast

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C29H24Cl2N2O7S
Molecular Weight	615.481
Optical Activity	( - )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CS(=O)(=O)C1=CC(C[C@H](NC(=O)C2=C(Cl)C3=C(CN(CC3)C(=O)C4=CC=C5C=COC5=C4)C=C2Cl)C(O)=O)=CC=C1

InChI

InChIKey=JFOZKMSJYSPYLN-QHCPKHFHSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208073s000lbl.pdf | https://clinicaltrials.gov/ct2/show/NCT00882687

Lifitegrast (under brand name Xiidra) was approved as an ophthalmic solution for the treatment of the signs and symptoms of dry eye disease. 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). This LFA-1/ICAM-1 interaction is a key step in the inflammatory cascade that contributes to dry eye disease. Besides lifitegrast participates in phase II clinical trials for prevention of the signs and symptoms of allergic conjunctivitis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Integrin alpha-L 4 Target ID: P20701 Gene ID: 3683.0 Gene Symbol: ITGAL Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27883115	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dry eye syndrome 21 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208073s000lbl.pdf	Primary		Approved 8429	XIIDRA Approved Use Xiidra™ (lifitegrast ophthalmic solution) 5% is indicated for the treatment of the signs and symptoms of dry eye disease (DED). Launch Date 2016
Allergic conjunctivitis 100 Sources: https://clinicaltrials.gov/ct2/show/NCT00882687	Preventing		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
126.383 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	5 % 3 times / day multiple, ocular dose: 5 % route of administration: Ocular experiment type: MULTIPLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
91.413 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	5 % 2 times / day multiple, ocular dose: 5 % route of administration: Ocular experiment type: MULTIPLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
10.756 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	0.3 % single, ocular dose: 0.3 % route of administration: Ocular experiment type: SINGLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
24.395 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	0.3 % 2 times / day multiple, ocular dose: 0.3 % route of administration: Ocular experiment type: MULTIPLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
27.457 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	1 % 3 times / day multiple, ocular dose: 1 % route of administration: Ocular experiment type: MULTIPLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
74.792 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	5 % single, ocular dose: 5 % route of administration: Ocular experiment type: SINGLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
16.222 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	1 % single, ocular dose: 1 % route of administration: Ocular experiment type: SINGLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
34.763 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	1 % 2 times / day multiple, ocular dose: 1 % route of administration: Ocular experiment type: MULTIPLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
7.49 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	0.3 % 3 times / day multiple, ocular dose: 0.3 % route of administration: Ocular experiment type: MULTIPLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
101.009 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	5 % 3 times / day multiple, ocular dose: 5 % route of administration: Ocular experiment type: MULTIPLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
127.594 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	5 % 2 times / day multiple, ocular dose: 5 % route of administration: Ocular experiment type: MULTIPLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.457 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	0.3 % single, ocular dose: 0.3 % route of administration: Ocular experiment type: SINGLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
24.793 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	0.3 % 2 times / day multiple, ocular dose: 0.3 % route of administration: Ocular experiment type: MULTIPLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
29.537 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	1 % 3 times / day multiple, ocular dose: 1 % route of administration: Ocular experiment type: MULTIPLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
311.929 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	5 % single, ocular dose: 5 % route of administration: Ocular experiment type: SINGLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
52.238 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	1 % single, ocular dose: 1 % route of administration: Ocular experiment type: SINGLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
62.443 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	1 % 2 times / day multiple, ocular dose: 1 % route of administration: Ocular experiment type: MULTIPLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
7.432 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20334535	0.3 % 3 times / day multiple, ocular dose: 0.3 % route of administration: Ocular experiment type: MULTIPLE co-administered:	LIFITEGRAST unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000ClinPharmR.pdf	unknown, ocular		LIFITEGRAST plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
5 % 2 times / day steady, ophthalmic Recommended Dose: 5 %, 2 times / day Route: ophthalmic Route: steady Dose: 5 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000MedR.pdf Page: p. 55	unhealthy, 58.6 years (range: 14 - 84 years) n = 355 Health Status: unhealthy Condition: dry eye disease Age Group: 58.6 years (range: 14 - 84 years) Sex: M+F Population Size: 355 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000MedR.pdf Page: p. 55	Disc. AE: Instillation site irritation, Headache... AEs leading to discontinuation/dose reduction: Instillation site irritation (1.1%) Headache (2 patients) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000MedR.pdf Page: p. 55
5 % 2 times / day steady, ophthalmic Recommended Dose: 5 %, 2 times / day Route: ophthalmic Route: steady Dose: 5 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000MedR.pdf Page: p. 55	unhealthy, 58.6 years (range: 14 - 84 years) n = 355 Health Status: unhealthy Condition: dry eye disease Age Group: 58.6 years (range: 14 - 84 years) Sex: M+F Population Size: 355 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000MedR.pdf Page: p. 55	Disc. AE: Instillation site reaction... AEs leading to discontinuation/dose reduction: Instillation site reaction (1.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000MedR.pdf Page: p. 55
5 % 2 times / day steady, ophthalmic Recommended Dose: 5 %, 2 times / day Route: ophthalmic Route: steady Dose: 5 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27055211	unhealthy, 58.8 years (range: 21 - 89 years( n = 220 Health Status: unhealthy Condition: dry eye disease Age Group: 58.8 years (range: 21 - 89 years( Sex: M+F Population Size: 220 Sources: https://pubmed.ncbi.nlm.nih.gov/27055211	Disc. AE: Lacrimation increased, Instillation site reaction... AEs leading to discontinuation/dose reduction: Lacrimation increased (1.4%) Instillation site reaction (1.8%) Visual acuity reduced (1.4%) Dysgeusia (1.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/27055211

AEs

AE	Significance	Dose	Population
Instillation site irritation	1.1% Disc. AE	5 % 2 times / day steady, ophthalmic Recommended Dose: 5 %, 2 times / day Route: ophthalmic Route: steady Dose: 5 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000MedR.pdf Page: p. 55	unhealthy, 58.6 years (range: 14 - 84 years) n = 355 Health Status: unhealthy Condition: dry eye disease Age Group: 58.6 years (range: 14 - 84 years) Sex: M+F Population Size: 355 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000MedR.pdf Page: p. 55
Headache	2 patients Disc. AE	5 % 2 times / day steady, ophthalmic Recommended Dose: 5 %, 2 times / day Route: ophthalmic Route: steady Dose: 5 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000MedR.pdf Page: p. 55	unhealthy, 58.6 years (range: 14 - 84 years) n = 355 Health Status: unhealthy Condition: dry eye disease Age Group: 58.6 years (range: 14 - 84 years) Sex: M+F Population Size: 355 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000MedR.pdf Page: p. 55
Instillation site reaction	1.4% Disc. AE	5 % 2 times / day steady, ophthalmic Recommended Dose: 5 %, 2 times / day Route: ophthalmic Route: steady Dose: 5 %, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000MedR.pdf Page: p. 55	unhealthy, 58.6 years (range: 14 - 84 years) n = 355 Health Status: unhealthy Condition: dry eye disease Age Group: 58.6 years (range: 14 - 84 years) Sex: M+F Population Size: 355 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000MedR.pdf Page: p. 55
Lacrimation increased	1.4% Disc. AE	5 % 2 times / day steady, ophthalmic Recommended Dose: 5 %, 2 times / day Route: ophthalmic Route: steady Dose: 5 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27055211	unhealthy, 58.8 years (range: 21 - 89 years( n = 220 Health Status: unhealthy Condition: dry eye disease Age Group: 58.8 years (range: 21 - 89 years( Sex: M+F Population Size: 220 Sources: https://pubmed.ncbi.nlm.nih.gov/27055211
Visual acuity reduced	1.4% Disc. AE	5 % 2 times / day steady, ophthalmic Recommended Dose: 5 %, 2 times / day Route: ophthalmic Route: steady Dose: 5 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27055211	unhealthy, 58.8 years (range: 21 - 89 years( n = 220 Health Status: unhealthy Condition: dry eye disease Age Group: 58.8 years (range: 21 - 89 years( Sex: M+F Population Size: 220 Sources: https://pubmed.ncbi.nlm.nih.gov/27055211
Dysgeusia	1.8% Disc. AE	5 % 2 times / day steady, ophthalmic Recommended Dose: 5 %, 2 times / day Route: ophthalmic Route: steady Dose: 5 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27055211	unhealthy, 58.8 years (range: 21 - 89 years( n = 220 Health Status: unhealthy Condition: dry eye disease Age Group: 58.8 years (range: 21 - 89 years( Sex: M+F Population Size: 220 Sources: https://pubmed.ncbi.nlm.nih.gov/27055211
Instillation site reaction	1.8% Disc. AE	5 % 2 times / day steady, ophthalmic Recommended Dose: 5 %, 2 times / day Route: ophthalmic Route: steady Dose: 5 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27055211	unhealthy, 58.8 years (range: 21 - 89 years( n = 220 Health Status: unhealthy Condition: dry eye disease Age Group: 58.8 years (range: 21 - 89 years( Sex: M+F Population Size: 220 Sources: https://pubmed.ncbi.nlm.nih.gov/27055211

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699	OATP1A2 62 OATP2B1 104

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000ClinPharmR.pdf#page=12 Page: 12.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000ClinPharmR.pdf#page=12 Page: 12.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	yes [IC50 4.1 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000ClinPharmR.pdf#page=11 Page: 11.0	yes [IC50 42 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OATP1A2 62	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000ClinPharmR.pdf#page=12 Page: 12.0	yes
OATP2B1 104	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208073Orig1s000ClinPharmR.pdf#page=12 Page: 12.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:133023	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:133023
ChemicalBook	CB92738258	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB92738258
MolPort	MolPort-044-727-763	https://www.molport.com/shop/molecule-link/MolPort-044-727-763
ZINC	ZINC000084668739	http://zinc15.docking.org/substances/ZINC000084668739

PubMed

Title	Date	PubMed
Tear cytokine profiles in dysfunctional tear syndrome.	2009 Feb	18992869
Liver X receptors as regulators of macrophage inflammatory and metabolic pathways.	2011 Aug	21193033
The pharmacologic assessment of a novel lymphocyte function-associated antigen-1 antagonist (SAR 1118) for the treatment of keratoconjunctivitis sicca in dogs.	2011 May 16	21330663
Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye.	2012 Mar 8	24900456
Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study.	2014 Feb	24289915

Patents

Sample Use Guides

In Vivo Use Guide

One drop twice daily in each eye (approximately 12 hours apart).

Route of Administration: Other

In Vitro Use Guide

Unknown

Name

Type

Language

Lifitegrast

Official Name

English

Lifitegrast [USAN]

Common Name

English

SHP-606

Code

English

Lifitegrast [INN]

Common Name

English

SAR-1118

Code

English

Lifitegrast [WHO-DD]

Common Name

English

Lifitegrast [ORANGE BOOK]

Common Name

English

Lifitegrast [MI]

Common Name

English

XIIDRA

Brand Name

English

SHP606

Code

English

(2S)-2-(((2-(benzofuran-6-ylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinolin-6-yl)carbonyl)amino)-3-(3-(methylsulfonyl)phenyl)propanoic acid

Systematic Name

English

L-Phenylalanine, N-[[2-(6-benzofuranylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydro-6-isoquinolinyl]carbonyl]-3-(methylsulfonyl)-

Systematic Name

English

SAR 1118

Code

English

Classification Tree Code System Code

WHO-ATC

S01XA25