darapladib   Click here for help

GtoPdb Ligand ID: 6696

Synonyms: SB 480848 | SB-480848
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Darapladib is a potent PLA2G7 (commonly referred to as Lp-PLA2) inhibitor. Darapladib and analogues such as rilapladib are clinical drug candidates with potential to reduce the risk of atherosclerosis and associated clinical sequelae [10].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 0
Rotatable bonds 15
Topological polar surface area 83.74
Molecular weight 666.27
XLogP 8.96
No. Lipinski's rules broken 2
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Canonical SMILES CCN(CCN(C(=O)Cn1c(SCc2ccc(cc2)F)nc(=O)c2c1CCC2)Cc1ccc(cc1)c1ccc(cc1)C(F)(F)F)CC
Isomeric SMILES CCN(CCN(C(=O)Cn1c(SCc2ccc(cc2)F)nc(=O)c2c1CCC2)Cc1ccc(cc1)c1ccc(cc1)C(F)(F)F)CC
InChI InChI=1S/C36H38F4N4O2S/c1-3-42(4-2)20-21-43(22-25-8-12-27(13-9-25)28-14-16-29(17-15-28)36(38,39)40)33(45)23-44-32-7-5-6-31(32)34(46)41-35(44)47-24-26-10-18-30(37)19-11-26/h8-19H,3-7,20-24H2,1-2H3
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Summary of Clinical Use Click here for help
This compound was being assessed in a Phase 3 clinical trial (NCT01067339) as a treatment for atherosclerosis, but it failed to meet clinical primary end points [4,6] and GSK has discontinued further development. Phase 2 trial results were published by Mohler et al. in 2008 [2].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
PLA2-G7 produced by macrophages in atherosclerotic plaques is implicated in the production of pro-inflammatory mediators that promote lesional inflammation and plaque growth and instability [5,8]. Selective PLA2-G7 inhibitors are thought to stabilise arterial plaques [3].