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Chemistry

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Also known as: 1025967-78-5, Xiidra, Sar 1118, Sar-1118, Shp606, Shp-606
Molecular Formula
C29H24Cl2N2O7S
Molecular Weight
615.5  g/mol
InChI Key
JFOZKMSJYSPYLN-QHCPKHFHSA-N
FDA UNII
038E5L962W

Lifitegrast
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.
Lifitegrast is a Lymphocyte Function-Associated Antigen-1 Antagonist. The mechanism of action of lifitegrast is as a Lymphocyte Function-Associated Antigen-1 Antagonist.
1 2D Structure

Lifitegrast

2 Identification
2.1 Computed Descriptors
2.1.1 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
2.1.2 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
2.1.3 InChI Key
JFOZKMSJYSPYLN-QHCPKHFHSA-N
2.1.4 Canonical SMILES
CS(=O)(=O)C1=CC=CC(=C1)CC(C(=O)O)NC(=O)C2=C(C=C3CN(CCC3=C2Cl)C(=O)C4=CC5=C(C=C4)C=CO5)Cl
2.1.5 Isomeric 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
2.2 Other Identifiers
2.2.1 UNII
038E5L962W
2.3 Synonyms
2.3.1 MeSH Synonyms

1. (2s)-2-(((2-(benzofuran-6-ylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinolin-6- Yl)carbonyl)amino)-3-(3-(methylsulfonyl)phenyl)propanoic Acid

2. L-phenylalanine, N-((2-(6-benzofuranylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydro-6-isoquinolinyl)carbonyl)-3-(methylsulfonyl)-

3. Lifitegrast Ophthalmic Solution

4. Sar 1118

5. Sar-1118

6. Shp-606

7. Shp606

8. Xiidra

2.3.2 Depositor-Supplied Synonyms

1. 1025967-78-5

2. Xiidra

3. Sar 1118

4. Sar-1118

5. Shp606

6. Shp-606

7. (s)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic Acid

8. Chembl2048028

9. 038e5l962w

10. (2s)-2-(((2-(benzofuran-6-ylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinolin-6- Yl)carbonyl)amino)-3-(3-(methylsulfonyl)phenyl)propanoic Acid

11. L-phenylalanine, N-((2-(6-benzofuranylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydro-6-isoquinolinyl)carbonyl)-3-(methylsulfonyl)-

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

13. Lifitegrast [usan:inn]

14. Unii-038e5l962w

15. Sar1118

16. Xiidra (tn)

17. Lifitegrast [mi]

18. Lifitegrast [inn]

19. Lifitegrast (usan/inn)

20. Lifitegrast [usan]

21. Lifitegrast; Sar 1118

22. Lifitegrast [who-dd]

23. Lifitegrast Ophthalmic Solution

24. Gtpl7533

25. Schembl2632068

26. Amy4450

27. Dtxsid60145345

28. Lifitegrast [orange Book]

29. Chebi:133023

30. Ex-a2582

31. Bdbm50386331

32. Mfcd28502439

33. S3714

34. Zinc84668739

35. Ccg-270245

36. Cs-6264

37. Db11611

38. Compound 1g [pmid: 24900456]

39. Ac-32534

40. Ds-20052

41. Hy-19344

42. D10374

43. A900838

44. Q23044263

45. (2s)-2-[[2-(1-benzofuran-6-carbonyl)-5,7-dichloro3,4-dihydro-1h-isoquinoline-6-carbonyl]amino]-3-(3-methylsulfonylphenyl)propanoic Acid

46. N-[[2-(6-benzofuranylcarbonyl)-5,7-dichloro-1,2,3,4-tetrahydro-6-isoquinolinyl]carbonyl]-3-(methylsulfonyl)-l-phenylalanine

47. N-[2-(1-benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carbonyl]-3-(methanesulfonyl)-l-phenylalanine

2.4 Create Date
2006-12-18
3 Chemical and Physical Properties
Molecular Weight 615.5 g/mol
Molecular Formula C29H24Cl2N2O7S
XLogP34.7
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count7
Rotatable Bond Count7
Exact Mass614.0681277 g/mol
Monoisotopic Mass614.0681277 g/mol
Topological Polar Surface Area142 Ų
Heavy Atom Count41
Formal Charge0
Complexity1100
Isotope Atom Count0
Defined Atom Stereocenter Count1
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

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


FDA Label


Treatment of dry eye disease


5 Pharmacology and Biochemistry
5.1 Pharmacology

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


5.2 MeSH Pharmacological Classification

Ophthalmic Solutions

Sterile solutions that are intended for instillation into the eye. It does not include solutions for cleaning eyeglasses or CONTACT LENS SOLUTIONS. (See all compounds classified as Ophthalmic Solutions.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
LIFITEGRAST
5.3.2 FDA UNII
038E5L962W
5.3.3 Pharmacological Classes
Lymphocyte Function-Associated Antigen-1 Antagonists [MoA]; Lymphocyte Function-Associated Antigen-1 Antagonist [EPC]
5.4 ATC Code

S - Sensory organs

S01 - Ophthalmologicals

S01X - Other ophthalmologicals

S01XA - Other ophthalmologicals

S01XA25 - Lifitegrast


5.5 Absorption, Distribution and Excretion

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. Observations show limited systemic exposure that produces significant clinical outcomes.


Route of Elimination

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


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. It is predicted that lifitegrast is cleared via nasal and subsequently gastrointestinal tract.


5.6 Metabolism/Metabolites

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


5.7 Biological 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.


5.8 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-, and IL-1 in human peripheral blood mononuclear cells.


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Drugs in Development

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Details:

Novartis will focus on other therapeutic areas, like retinal diseases via platforms including gene therapy and optogenetics through divestment of Xiidra (lifitegrast), the first approved treatment for dry eye disease, and SAF312 (libvatrep), for chronic ocular surface pain.


Lead Product(s): Lifitegrast

Therapeutic Area: Ophthalmology Brand Name: Xiidra

Study Phase: ApprovedProduct Type: Small molecule

Sponsor: Bausch & Lomb Incorporated

Deal Size: $2,500.0 million Upfront Cash: $1,750.0 million

Deal Type: Divestment September 29, 2023

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AES 2024
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AES 2024
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Details : Novartis will focus on other therapeutic areas, like retinal diseases via platforms including gene therapy and optogenetics through divestment of Xiidra (lifitegrast), the first approved treatment for dry eye disease, and SAF312 (libvatrep), for chronic ...

Brand Name : Xiidra

Molecule Type : Small molecule

Upfront Cash : $1,750.0 million

September 29, 2023

blank

Details:

The financing will fund the acquisition Xiidra (lifitegrast ophthalmic solution), a non-steroid eye drop specifically approved to treat the signs and symptoms of dry eye disease focusing on inflammation associated with dry eye, and certain other ophthalmology assets.


Lead Product(s): Lifitegrast

Therapeutic Area: Ophthalmology Brand Name: Xiidra

Study Phase: ApprovedProduct Type: Small molecule

Sponsor: Undisclosed

Deal Size: Undisclosed Upfront Cash: Undisclosed

Deal Type: Financing September 11, 2023

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02

AES 2024
Not Confirmed
AES 2024
Not Confirmed

Details : The financing will fund the acquisition Xiidra (lifitegrast ophthalmic solution), a non-steroid eye drop specifically approved to treat the signs and symptoms of dry eye disease focusing on inflammation associated with dry eye, and certain other ophthalm...

Brand Name : Xiidra

Molecule Type : Small molecule

Upfront Cash : Undisclosed

September 11, 2023

blank

Details:

Novartis will focus on other therapeutic areas, like retinal diseases via platforms including gene therapy and optogenetics through divestment of Xiidra (lifitegrast), the first approved treatment for dry eye disease, and SAF312 (libvatrep), for chronic ocular surface pain.


Lead Product(s): Lifitegrast

Therapeutic Area: Ophthalmology Brand Name: Xiidra

Study Phase: ApprovedProduct Type: Small molecule

Sponsor: Bausch & Lomb Incorporated

Deal Size: $2,500.0 million Upfront Cash: $1,750.0 million

Deal Type: Divestment June 30, 2023

blank

03

AES 2024
Not Confirmed
AES 2024
Not Confirmed

Details : Novartis will focus on other therapeutic areas, like retinal diseases via platforms including gene therapy and optogenetics through divestment of Xiidra (lifitegrast), the first approved treatment for dry eye disease, and SAF312 (libvatrep), for chronic ...

Brand Name : Xiidra

Molecule Type : Small molecule

Upfront Cash : $1,750.0 million

June 30, 2023

blank

Details:

Novartis intends to develop the AcuStream technology for potential use with its existing and future front-of-eye therapies, which could include Xiidra® (lifitegrast ophthalmic solution) 5%, a first-in-class prescription LFA 1 antagonist for the treatment of dry eye disease.


Lead Product(s): Lifitegrast

Therapeutic Area: Ophthalmology Brand Name: Xiidra

Study Phase: ApprovedProduct Type: Small molecule

Sponsor: Novartis Pharmaceuticals Corporation

Deal Size: Undisclosed Upfront Cash: Undisclosed

Deal Type: Acquisition June 30, 2022

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AES 2024
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AES 2024
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Details : Novartis intends to develop the AcuStream technology for potential use with its existing and future front-of-eye therapies, which could include Xiidra® (lifitegrast ophthalmic solution) 5%, a first-in-class prescription LFA 1 antagonist for the treatmen...

Brand Name : Xiidra

Molecule Type : Small molecule

Upfront Cash : Undisclosed

June 30, 2022

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Regulatory Info :

Registration Country : Greece

Lifitegrast

Brand Name :

Dosage Form : Ophthalmic Solution

Dosage Strength : 50MG/ML

Packaging :

Approval Date :

Application Number :

Regulatory Info :

Registration Country : Greece

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LIFITEGRAST

Brand Name : LIFITEGRAST

Dosage Form : SOLUTION/DROPS;OPHTHALMIC

Dosage Strength : 5%

Packaging :

Approval Date : 2024-10-03

Application Number : 215058

Regulatory Info : RX

Registration Country : USA

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LIFITEGRAST

Brand Name : LIFITEGRAST

Dosage Form : SOLUTION/DROPS;OPHTHALMIC

Dosage Strength : 5%

Packaging :

Approval Date : 2023-11-07

Application Number : 215063

Regulatory Info : DISCN

Registration Country : USA

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LIFITEGRAST

Brand Name : XIIDRA

Dosage Form : SOLUTION/DROPS;OPHTHALMIC

Dosage Strength : 5%

Packaging :

Approval Date : 2016-07-11

Application Number : 208073

Regulatory Info : RX

Registration Country : USA

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LIFITEGRAST

Brand Name : LIFITEGRAST

Dosage Form : SOLUTION/DROPS;OPHTHALMIC

Dosage Strength : 5%

Packaging :

Approval Date : 2023-08-04

Application Number : 215081

Regulatory Info : DISCN

Registration Country : USA

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LIFITEGRAST

Brand Name : XIIDRA

Dosage Form : SOLUTION

Dosage Strength : 5%/W/V

Packaging :

Approval Date :

Application Number : 2471027

Regulatory Info : Prescription

Registration Country : Canada

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LIFITEGRAST

Brand Name : LIFITEGRAST

Dosage Form : SOLUTION/DROPS;OPHTHALMIC

Dosage Strength : 5%

Packaging :

Approval Date :

Application Number : 215126

Regulatory Info :

Registration Country : USA

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LIFITEGRAST

Brand Name : LIFITEGRAST

Dosage Form : SOLUTION/DROPS;OPHTHALMIC

Dosage Strength : 5%

Approval Date : 2024-10-03

Application Number : 215058

RX/OTC/DISCN : RX

RLD : No

TE Code : AB

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EUGIA PHARMA

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EUGIA PHARMA

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LIFITEGRAST

Brand Name : LIFITEGRAST

Dosage Form : SOLUTION/DROPS;OPHTHALMIC

Dosage Strength : 5%

Approval Date : 2023-11-07

Application Number : 215063

RX/OTC/DISCN : DISCN

RLD : No

TE Code :

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LIFITEGRAST

Brand Name : XIIDRA

Dosage Form : SOLUTION/DROPS;OPHTHALMIC

Dosage Strength : 5%

Approval Date : 2016-07-11

Application Number : 208073

RX/OTC/DISCN : RX

RLD : Yes

TE Code : AB

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04

MICRO LABS

India
Pharma, Lab & Chemical Expo
Not Confirmed
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MICRO LABS

India
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Pharma, Lab & Chemical Expo
Not Confirmed

LIFITEGRAST

Brand Name : LIFITEGRAST

Dosage Form : SOLUTION/DROPS;OPHTHALMIC

Dosage Strength : 5%

Approval Date : 2023-08-04

Application Number : 215081

RX/OTC/DISCN : DISCN

RLD : No

TE Code :

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05

Pharma, Lab & Chemical Expo
Not Confirmed
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Pharma, Lab & Chemical Expo
Not Confirmed

LIFITEGRAST

Brand Name : LIFITEGRAST

Dosage Form : SOLUTION/DROPS;OPHTHALMIC

Dosage Strength : 5%

Approval Date :

Application Number : 215126

RX/OTC/DISCN :

RLD :

TE Code :

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Canada

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01

Pharma, Lab & Chemical Expo
Not Confirmed
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Pharma, Lab & Chemical Expo
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LIFITEGRAST

Brand Name : XIIDRA

Dosage Form : SOLUTION

Dosage Strength : 5%/W/V

Packaging :

Approval Date :

Application Number : 2471027

Regulatory Info : Prescription

Registration Country : Canada

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Listed Dossiers

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Pharmathen SA

Greece
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Pharma, Lab & Chemical Expo
Not Confirmed
  • fda
  • EDQM
  • WHO-GMP

Virtual BoothPharmathen provides life cycle Management solutions for branded pharma, as well as to develop & establish new technology platforms.

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Regulatory Info :

Registration Country : Greece

Lifitegrast

Brand Name :

Dosage Form : Ophthalmic Solution

Dosage Strength : 50MG/ML

Packaging :

Approval Date :

Application Number :

Regulatory Info :

Registration Country : Greece

Pharmathen

01

Pharmathen SA

Greece
arrow
Pharma, Lab & Chemical Expo
Not Confirmed
  • fda
  • EDQM
  • WHO-GMP

Virtual BoothPharmathen provides life cycle Management solutions for branded pharma, as well as to develop & establish new technology platforms.

Flag Greece
Digital Content Digital Content

Packaging :

Regulatory Info :

Lifitegrast

Dosage : Ophthalmic Solution

Dosage Strength : 50MG/ML

Brand Name :

Approval Date :

Application Number :

Registration Country : Greece

Pharmathen
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