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].
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2D Structure
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Physico-chemical Properties
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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
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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
Bioactivity Comments
No specific binding data are provided in [9] to substantiate the lifitegrast/LFA-1 interaction. Target engagement is inferred from biological assays showing inhibition of T cell adhesion and inhibition of inflammatory mediator secretion. In in vitro assays, lifitegrast inhibits Jurkat T cell and HuT 78 T cell adhesion to immobilised ICAM-Ig with IC50s of 2.98nM and 9nM respectively [9].
Lifitegrast was designed to have minimal systemic exposure, to limit action at sites other than at the site of administration [7].
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide) Primary target of this compound Hs Antagonist Inhibition - - - 2,9