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/)
Immunopharmacology Comments
Chronic inflammation is an important factor in the pathogenesis of dry eye. Lymphocyte function-associated antigen-1 [LFA-1, αLβ2, or (CD11a)/CD18] is a heterodimeric β2 integrin. Its interactions with intercellular adhesion molecule-1 (ICAM-1 or CD54) are critical to the adhesion, migration, and proliferation of T-cells at the inflammation sites and T-cell specific immune responses. LFA-1 antagonism of ICAM-1 as demonstrated by lifitegrast, is thus now a successful anti-inflammatory treatment [9]
Immunopharmacology Disease
Disease X-Refs Comment References
keratoconjunctivitis sicca Disease Ontology: DOID:12895
 Approved drug for keratoconjunctivitis sicca.