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].
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. 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.

✖
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
SMILES / InChI / InChIKey
Click here for help

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.

✖
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
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
⤷ [2,9]