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

SMILES

CS(=O)(=O)C1=CC(C[C@H](NC(=O)C2=C(Cl)C3=C(CN(CC3)C(=O)C4=CC5=C(C=CO5)C=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

Molecular Formula	C29H24Cl2N2O7S
Molecular Weight	615.481
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

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	Antagonist 2,849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dry eye syndrome 21	Primary		Approved 8,583	XIIDRA
Allergic conjunctivitis 101	Preventing		Phase II 1,147	Unknown

C_max

Value	Dose	Analyte	Population
74.792 ng/mL	5 % single, ocular	LIFITEGRAST aqueous humor	Homo sapiens
91.413 ng/mL	5 % 2 times / day multiple, ocular	LIFITEGRAST aqueous humor	Homo sapiens
126.383 ng/mL	5 % 3 times / day multiple, ocular	LIFITEGRAST aqueous humor	Homo sapiens
16.222 ng/mL	1 % single, ocular	LIFITEGRAST aqueous humor	Homo sapiens
34.763 ng/mL	1 % 2 times / day multiple, ocular	LIFITEGRAST aqueous humor	Homo sapiens
27.457 ng/mL	1 % 3 times / day multiple, ocular	LIFITEGRAST aqueous humor	Homo sapiens
10.756 ng/mL	0.3 % single, ocular	LIFITEGRAST aqueous humor	Homo sapiens
24.395 ng/mL	0.3 % 2 times / day multiple, ocular	LIFITEGRAST aqueous humor	Homo sapiens
7.49 ng/mL	0.3 % 3 times / day multiple, ocular	LIFITEGRAST aqueous humor	Homo sapiens

AUC

Value	Dose	Analyte	Population
311.929 ng × h/mL	5 % single, ocular	LIFITEGRAST aqueous humor	Homo sapiens
127.594 ng × h/mL	5 % 2 times / day multiple, ocular	LIFITEGRAST aqueous humor	Homo sapiens
101.009 ng × h/mL	5 % 3 times / day multiple, ocular	LIFITEGRAST aqueous humor	Homo sapiens
52.238 ng × h/mL	1 % single, ocular	LIFITEGRAST aqueous humor	Homo sapiens
62.443 ng × h/mL	1 % 2 times / day multiple, ocular	LIFITEGRAST aqueous humor	Homo sapiens
29.537 ng × h/mL	1 % 3 times / day multiple, ocular	LIFITEGRAST aqueous humor	Homo sapiens
2.457 ng × h/mL	0.3 % single, ocular	LIFITEGRAST aqueous humor	Homo sapiens
24.793 ng × h/mL	0.3 % 2 times / day multiple, ocular	LIFITEGRAST aqueous humor	Homo sapiens
7.432 ng × h/mL	0.3 % 3 times / day multiple, ocular	LIFITEGRAST aqueous humor	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
1%	unknown, ocular		LIFITEGRAST plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
5 % 2 times / day steady, ophthalmic Recommended	unhealthy, 58.6 years (range: 14 - 84 years)	Disc. AE: Instillation site irritation, Headache...
5 % 2 times / day steady, ophthalmic Recommended	unhealthy, 58.6 years (range: 14 - 84 years)	Disc. AE: Instillation site reaction...
5 % 2 times / day steady, ophthalmic Recommended	unhealthy, 58.8 years (range: 21 - 89 years(	Disc. AE: Lacrimation increased, Instillation site reaction...

Showing 1 to 3 of 3 entries

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AEs

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AE	Significance	Dose	Population
Instillation site irritation	1.1% Disc. AE	5 % 2 times / day steady, ophthalmic Recommended	unhealthy, 58.6 years (range: 14 - 84 years)
Headache	2 patients Disc. AE	5 % 2 times / day steady, ophthalmic Recommended	unhealthy, 58.6 years (range: 14 - 84 years)
Instillation site reaction	1.4% Disc. AE	5 % 2 times / day steady, ophthalmic Recommended	unhealthy, 58.6 years (range: 14 - 84 years)
Lacrimation increased	1.4% Disc. AE	5 % 2 times / day steady, ophthalmic Recommended	unhealthy, 58.8 years (range: 21 - 89 years(
Visual acuity reduced	1.4% Disc. AE	5 % 2 times / day steady, ophthalmic Recommended	unhealthy, 58.8 years (range: 21 - 89 years(

Showing 1 to 5 of 7 entries

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2,252	inhibitor 2,438

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1,741 BCRP 910	OATP1A2 67 OATP2B1 122

Drug as perpetrator

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Target	Modality	Activity
BCRP 985	inhibitor 4,027	no
P-gp 1,932	inhibitor 4,027	no
CYP2C9 2,497	inhibitor 4,027	yes [IC50 4.1 uM]
CYP3A4 2,633	inhibitor 4,027	yes [IC50 42 uM]

Showing 1 to 4 of 4 entries

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Drug as victim

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Target	Modality	Activity	Metabolite	Clinical evidence
OATP1A2 67	substrate 4,014	yes
OATP2B1 122	substrate 4,014	yes

Showing 1 to 2 of 2 entries

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Sourcing

Sourcing

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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