lifitegrast   Click here for help

GtoPdb Ligand ID: 7533

Synonyms: compound 1g [PMID: 24900456] | SAR 1118 | SAR-1118 | SAR-1118-023 | Xiidra®
Approved drug Immunopharmacology Ligand
lifitegrast is an approved drug (FDA (2016))
Compound class: Synthetic organic
Comment: It is postulated that lifitegrast (SAR 1118) interacts with the lymphocyte function-associated antigen-1 (LFA-1) to inhbit the LFA-1/ICAM-1 adhesion interaction and was approved for the treatment of Dry Ey in 2016 [7,9]. LFA-1 is a heterodimeric member of the β2 integrin family which is essential for adhesion, migration, and proliferation of T cells at sites of inflammation, and is involved in T cell specific immune responses through the formation of adhesive interactions and immunological synapses. Intercellular adhesion molecule‑1 (ICAM‑1) is the cognate ligand of LFA-1.The compound formulation is claimed in patent WO2014100135 [7].

lifitegrast is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 142.37
Molecular weight 614.07
XLogP 4.69
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES OC(=O)C(NC(=O)c1c(Cl)cc2c(c1Cl)CCN(C2)C(=O)c1ccc2c(c1)occ2)Cc1cccc(c1)S(=O)(=O)C
Isomeric SMILES OC(=O)[C@@H](NC(=O)c1c(Cl)cc2c(c1Cl)CCN(C2)C(=O)c1ccc2c(c1)occ2)Cc1cccc(c1)S(=O)(=O)C
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
InChI Key JFOZKMSJYSPYLN-QHCPKHFHSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. A-González N, Castrillo A. (2011)
Liver X receptors as regulators of macrophage inflammatory and metabolic pathways.
Biochim Biophys Acta, 1812 (8): 982-94. [PMID:21193033]
2. Breitenstein W, Huerzeler M, Kelly T, Mancuso R, Schneider G, Weitz-Schmidt G. (2015)
Small molecule lfa-1 inhibitors.
Patent number: WO2015189265. Assignee: Allocyte Pharmaceuticals Ag. Priority date: 12/06/2014. Publication date: 17/12/2015.
3. Giblin PA, Lemieux RM. (2006)
LFA-1 as a key regulator of immune function: approaches toward the development of LFA-1-based therapeutics.
Curr Pharm Des, 12 (22): 2771-95. [PMID:16918410]
4. Kapp TG, Rechenmacher F, Sobahi TR, Kessler H. (2013)
Integrin modulators: a patent review.
Expert Opin Ther Pat, 23 (10): 1273-95. [PMID:24050747]
5. Lam H, Bleiden L, de Paiva CS, Farley W, Stern ME, Pflugfelder SC. (2009)
Tear cytokine profiles in dysfunctional tear syndrome.
Am J Ophthalmol, 147 (2): 198-205. e1. [PMID:18992869]
6. Murphy CJ, Bentley E, Miller PE, McIntyre K, Leatherberry G, Dubielzig R, Giuliano E, Moore CP, Phillips TE, Smith PB et al.. (2011)
The pharmacologic assessment of a novel lymphocyte function-associated antigen-1 antagonist (SAR 1118) for the treatment of keratoconjunctivitis sicca in dogs.
Invest Ophthalmol Vis Sci, 52 (6): 3174-80. [PMID:21330663]
7. Newman M, Hunke W. (2014)
Lfa-1 inhibitor formulations.
Patent number: WO2014100135. Assignee: Sarcode Bioscience Inc.. Priority date: 19/12/2012. Publication date: 26/06/2014.
8. Sheppard JD, Torkildsen GL, Lonsdale JD, D'Ambrosio Jr FA, McLaurin EB, Eiferman RA, Kennedy KS, Semba CP, OPUS-1 Study Group. (2014)
Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study.
Ophthalmology, 121 (2): 475-83. [PMID:24289915]
9. Zhong M, Gadek TR, Bui M, Shen W, Burnier J, Barr KJ, Hanan EJ, Oslob JD, Yu CH, Zhu J et al.. (2012)
Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye.
ACS Med Chem Lett, 3 (3): 203-6. [PMID:24900456]