Darapladib

Summary

Darapladib (CHEMBL204021) is a phase-3 clinical-stage small molecule targeting PLA2G7; indicated across 3 conditions including atherosclerosis and acute coronary syndrome.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (PLA2G7)
• Indications: 3 conditions
• Clinical trials: 20
• Chemistry: 666.8 Da · C36H38F4N4O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL204021
Name	Darapladib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	9939609
Molecular formula	C36H38F4N4O2S
Molecular weight	666.8
InChIKey	WDPFJWLDPVQCAJ-UHFFFAOYSA-N

SMILES: CCN(CC)CCN(CC1=CC=C(C=C1)C2=CC=C(C=C2)C(F)(F)F)C(=O)CN3C4=C(CCC4)C(=O)N=C3SCC5=CC=C(C=C5)F

IUPAC name: N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide

Also known as: Darapladib, SB-480848, DARAPLADIB

Parent form; salt/anhydrous children: CHEMBL3793364

Patent coverage: 166 distinct patent families (370 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
PLA2G7	PLA2-G7	Inhibition	10.31	0.7%	Q13093

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Cytochrome P450 2D6, Cytochrome P450 3A4, Platelet-activating factor acetylhydrolase.

Bioactivity

ChEMBL activities: 15 potent at pChembl ≥ 5 of 17 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PLA2G7	10.31	IC50	0.05	nM	CHEMBL_ACT_16620076
PLA2G7	10.31	IC50	0.05	nM	CHEMBL_ACT_16759632
PLA2G7	10.31	IC50	0.05	nM	CHEMBL_ACT_16759672
PLA2G7	10.2	IC50	0.06	nM	CHEMBL_ACT_16813500
PLA2G7	10	IC50	0.1	nM	CHEMBL_ACT_13301366
PLA2G7	9.96	Ki	0.11	nM	CHEMBL_ACT_132014
PLA2G7	9.6	IC50	0.25	nM	CHEMBL_ACT_132013
PLA2G7	9.6	IC50	0.25	nM	CHEMBL_ACT_15765073
PLA2G7	9.6	IC50	0.25	nM	CHEMBL_ACT_18492048
PLA2G7	9.22	IC50	0.6	nM	CHEMBL_ACT_18123041
PLA2G7	9.15	IC50	0.7	nM	CHEMBL_ACT_15765020
PLA2G7	9.15	IC50	0.7	nM	CHEMBL_ACT_16555249
PLA2G7	8.3	IC50	5	nM	CHEMBL_ACT_132015
PLA2G7	7.46	IC50	35	nM	CHEMBL_ACT_16620094
PLA2G7	7.3	Kd	49.7	nM	CHEMBL_ACT_16654934

Target pathways

Aggregated over 1 target gene(s): PLA2G7.

Top Reactome pathways

1 total, by targets touching each:

Pathway	Targets	Genes
Synthesis, secretion, and deacylation of Ghrelin	1	PLA2G7

Dominant GO biological processes

GO term	Targets
peptide hormone processing	1
low-density lipoprotein particle remodeling	1
lipid oxidation	1
plasma lipoprotein particle oxidation	1
phosphatidylcholine catabolic process	1
platelet activating factor metabolic process	1
positive regulation of inflammatory response	1
platelet activating factor catabolic process	1
positive regulation of monocyte chemotaxis	1
lipid metabolic process	1
phospholipid catabolic process	1
lipid catabolic process	1

Indications & clinical

Indications

3 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
atherosclerosis	3	MONDO:0005311	EFO:0003914
acute coronary syndrome	3	MONDO:0005542	EFO:0005672
diabetic retinopathy	2	MONDO:0005266	EFO:0003770

Clinical trials

Total trials: 20.

Phase distribution

Phase	Trials
PHASE1	12
PHASE2	4
PHASE3	3
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00799903	PHASE3	COMPLETED	The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial
NCT01000727	PHASE3	COMPLETED	The Stabilization Of pLaques usIng Darapladib-Thrombolysis In Myocardial Infarction 52 Trial
NCT01067339	PHASE3	COMPLETED	Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Progenitor Cells and Coronary Atherosclerosis in Humans
NCT00268996	PHASE2	COMPLETED	Integrated Biomarker And Imaging Study - 2
NCT00269048	PHASE2	COMPLETED	SB-480848 In Subjects With Coronary Heart Disease
NCT01506895	PHASE2	COMPLETED	A Phase 2 Clinical Study to Investigate Effects of Darapladib in Subjects With Diabetic Macular Edema
NCT01916720	PHASE2	COMPLETED	Study to Determine the Effect of 14 Days Dosing With Darapladib (SB-480848) on Carotid Plague Composition in Patients With Planned Carotid Endarterectomy
NCT00411073	PHASE1	COMPLETED	Study Of The Effects Of SB 480848 (Darapladib) On The Electrical Conduction Of The Heart
NCT00551317	PHASE1	COMPLETED	A Study Investigating the Concentrations of Darapladib in Blood and the Safety of This Compound in Healthy Japanese Men
NCT00622830	PHASE1	COMPLETED	Phase I Study of SB-480848(Darapladib) -Repeat Dose Study in Healthy Japanese Male Subjects-
NCT00704431	PHASE1	COMPLETED	A Study With Darapladib to Collect Tolerability Information
NCT00743860	PHASE1	COMPLETED	A Healthy Volunteer Pharmacokinetic Study of Single and Repeat Doses of SB-480848
NCT01154114	PHASE1	COMPLETED	Study to Evaluate Darapladib in Moderately Hepatically Impaired Subjects
NCT01711723	PHASE1	COMPLETED	A Study to Assess the Pharmacokinetics, Safety and Tolerability of Repeat Oral Doses of Darapladib (SB-480848) in Subjects With Severe Renal Impairment
NCT01751074	PHASE1	COMPLETED	To Estimate the Potential Effects of Repeat Doses of Darapladib on the Pharmacokinetics (PK) of Rosuvastatin as Well as Evaluating Safety and Tolerability in Healthy Volunteers
NCT01852565	PHASE1	COMPLETED	Study to Determine the Effect of Repeated Administration of Diltiazem on the Pharmacokinetics of Darapladib (Sb-480848).
NCT01873339	PHASE1	COMPLETED	Pharmacokinetic Interaction of Darapladib and CYP 3A4 in Healthy Subjects
NCT02000804	PHASE1	COMPLETED	Darapladib China PK
NCT02058641	PHASE1	COMPLETED	Effect of Darapladib on Cantharidin-Induced Inflammatory Blisters in Subjects With Type 2 Diabetes Mellitus (T2DM)
NCT01636271	Not specified	COMPLETED	SB-480848 in Major Adverse Cardiovascular Events - Integrated Summary of Efficacy and Safety From the STABILITY Trial (LPL100601) and the SOLID-TIMI-52 Trial (SB-480848/033)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 7 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

6 molecules share ≥1 primary target. Top 6 by shared-target count:

Molecule	Source	Status	Shared targets
ORLISTAT	ChEMBL + PubChem	Phase 4 (approved)	PLA2G7
RILAPLADIB	ChEMBL	Phase 2	PLA2G7
Caffeic Acid	PubChem	Approved	PLA2G7
Chlorogenic Acid	PubChem	Approved	PLA2G7
Gallic Acid	PubChem	Approved	PLA2G7
oxyquinoline	PubChem	Approved	PLA2G7