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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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.

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View interactive charts of activity data across species

darapladib 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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Click here for structure editor
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 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.

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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
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.

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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
InChI Key WDPFJWLDPVQCAJ-UHFFFAOYSA-N
References
1. Blackie JA, Bloomer JC, Brown MJ, Cheng HY, Hammond B, Hickey DM, Ife RJ, Leach CA, Lewis VA, Macphee CH et al.. (2003)
The identification of clinical candidate SB-480848: a potent inhibitor of lipoprotein-associated phospholipase A2.
Bioorg Med Chem Lett, 13 (6): 1067-70. [PMID:12643913]
2. Mohler 3rd ER, Ballantyne CM, Davidson MH, Hanefeld M, Ruilope LM, Johnson JL, Zalewski A, Darapladib Investigators. (2008)
The effect of darapladib on plasma lipoprotein-associated phospholipase A2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent: the results of a multicenter, randomized, double-blind, placebo-controlled study.
J Am Coll Cardiol, 51 (17): 1632-41. [PMID:18436114]
3. O'Donoghue ML, Braunwald E, White HD, Serruys P, Steg PG, Hochman J, Maggioni AP, Bode C, Weaver D, Johnson JL et al.. (2011)
Study design and rationale for the Stabilization of pLaques usIng Darapladib-Thrombolysis in Myocardial Infarction (SOLID-TIMI 52) trial in patients after an acute coronary syndrome.
Am Heart J, 162 (4): 613-619.e1. [PMID:21982651]
4. O'Donoghue ML, Braunwald E, White HD, Steen DP, Lukas MA, Tarka E, Steg PG, Hochman JS, Bode C, Maggioni AP et al.. (2014)
Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial.
JAMA, 312 (10): 1006-15. [PMID:25173516]
5. Sofogianni A, Alkagiet S, Tziomalos K. (2018)
Lipoprotein-associated Phospholipase A2 and Coronary Heart Disease.
Curr Pharm Des, 24 (3): 291-296. [PMID:29332572]
6. STABILITY Investigators, White HD, Held C, Stewart R, Tarka E, Brown R, Davies RY, Budaj A, Harrington RA, Steg PG et al.. (2014)
Darapladib for preventing ischemic events in stable coronary heart disease.
N Engl J Med, 370 (18): 1702-11. [PMID:24678955]
7. Staurenghi G, Ye L, Magee MH, Danis RP, Wurzelmann J, Adamson P, McLaughlin MM, Darapladib DME Study Group. (2015)
Darapladib, a lipoprotein-associated phospholipase A2 inhibitor, in diabetic macular edema: a 3-month placebo-controlled study.
Ophthalmology, 122 (5): 990-6. [PMID:25749297]
8. Tian Y, Jia H, Li S, Wu Y, Guo L, Tan G, Li B. (2017)
The associations of stroke, transient ischemic attack, and/or stroke-related recurrent vascular events with Lipoprotein-associated phospholipase A2: A systematic review and meta-analysis.
Medicine (Baltimore), 96 (51): e9413. [PMID:29390564]
9. Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, Hooper S, Le Trong H, Cousens LS, Zimmerman GA et al.. (1995)
Anti-inflammatory properties of a platelet-activating factor acetylhydrolase.
Nature, 374 (6522): 549-53. [PMID:7700381]
10. Wilensky RL, Macphee CH. (2009)
Lipoprotein-associated phospholipase A(2) and atherosclerosis.
Curr Opin Lipidol, 20 (5): 415-20. [PMID:19667981]
11. Woolford AJ, Day PJ, Bénéton V, Berdini V, Coyle JE, Dudit Y, Grondin P, Huet P, Lee LY, Manas ES et al.. (2016)
Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA2).
J Med Chem, 59 (23): 10738-10749. [PMID:27933945]