DARAPLADIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C36H38F4N4O2S
Molecular Weight	666.771
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

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(F)C=C5

InChI

InChIKey=WDPFJWLDPVQCAJ-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15957087
Curator's Comment: description was created based on several sources, including http://www.fiercebiotech.com/r-d/updated-glaxosmithkline-loses-its-first-big-phiii-bet-on-heart-drug-darapladib

Darapladib (SB-435495), as reversible inhibitors of lipoprotein-associated phospholipase A(2) (Lp-PLA(2) has been developed and studies for the potential treatment of atherosclerosis. In November 2013, GSK announced that the drug had failed to meet Phase III endpoints in a trial of 16,000 patients with acute coronary syndrome.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
LDL-associated phospholipase A2 2 Target ID: CHEMBL3514 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12643913	Inhibitor 8297		0.25 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Atherosclerosis 74 Sources: https://clinicaltrials.gov/ct2/show/NCT00799903	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
34.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26465780	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:		DARAPLADIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
17.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26465780	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:		DARAPLADIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
519 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26465780	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:		DARAPLADIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
645 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26465780	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:		DARAPLADIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
116 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26465780	160 mg 1 times / day multiple, oral dose: 160 mg route of administration: Oral experiment type: MULTIPLE co-administered:		DARAPLADIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
39.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26465780	160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered:		DARAPLADIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
160 mg 1 times / day multiple, oral Studied dose Dose: 160 mg, 1 times / day Route: oral Route: multiple Dose: 160 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26465780 Page: p.10	healthy, ADULT n = 24 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FED Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/26465780 Page: p.10	Sources: https://pubmed.ncbi.nlm.nih.gov/26465780 Page: p.10

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P003PPF	https://www.1pchem.com/search?query=1P003PPF
AChemBlock	C-2941	http://www.achemblock.com/catalogsearch/result/?q=C-2941
AK Scientific	SYN5724	https://aksci.com/item_detail.php?cat=SYN5724
AK Scientific	X5943	https://aksci.com/item_detail.php?cat=X5943
AOBIOUS INC	AOB87381	http://aobious.com/aobious/search?search_query=AOB87381
Aceschem	ACF022796	https://www.aceschem.com/catalog/search.do?q=ACF022796
Angene	AGN-PC-0RB47J	http://www.angenechemical.com/productshow/AGN-PC-0RB47J.html
ApexBio Technology	A3349	https://www.apexbt.com/catalogsearch/result/?q=A3349
AstaTech	FD5008	http://astatechinc.com/CPSResult.php?CRNO=FD5008
BLD Pharm	BD301648	http://www.bldpharm.com/search/Search.html?keyword=BD301648
BOC Sciences	356057-34-6	http://www.bocsci.com/description.asp?cas=356057-34-6
Cayman Chemical	16429	http://www.caymanchem.com/app/template/Product.vm/catalog/16429
Chem Scene	CS-1035	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1035
ChemShuttle	113947	https://www.chemshuttle.com/catalogsearch/result/?q=113947
Combi-Blocks	QM-5328	http://www.combi-blocks.com/cgi-bin/find.cgi?QM-5328
Excenen	EX-A2245	http://www.excenen.com/searchresultlist.php?id=EX-A2245
KeyOrganics	AS-17025	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17025
Lab Seeker	SC-94293	http://www.labseeker.com/search.php?keywords=SC-94293&category=0
LabSeeker	SC-94293	http://www.labseeker.com/search.php?keywords=SC-94293&category=0
Matrix Scientific	147917	http://www.matrixscientific.com/147917.html
MedChem Express	HY-10521	https://www.medchemexpress.com/search.html?q=HY-10521&ft=&fa=&fp=
MolPort	MolPort-019-996-296	https://www.molport.com/shop/molecule-link/MolPort-019-996-296
Molnova	M14219	https://www.molnova.com/en/serch-list.html?keywords=M14219
MuseChem	I003299	https://www.musechem.com/product/I003299.html
Selleck Chemicals	S7520	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7520
ShangHai Biochempartner	BCP000587	http://www.biochempartner.com/search_BCP000587
ShangHai Biochempartner	BCP04908	http://www.biochempartner.com/search_BCP04908
Synthonix	1602	https://synthonix.com/catalogsearch/result/?q=1602
TargetMol	T6109	https://www.targetmol.com/search?keyword=T6109
Tetrahedron	TS90555	http://www.thsci.com/search.do?q=TS90555
eMolecules	43367244	https://orderbb.emolecules.com/search/#?query=43367244
eNovation Chemicals	D498184	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D498184&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-4205270723	https://mcule.com/MCULE-4205270723/

PubMed

Title	Date	PubMed
Gateways to clinical trials.	2008 Apr	18597009
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.	2008 Apr 29	18436114
Inhibition of lipoprotein-associated phospholipase activity by darapladib: shifting gears in cardiovascular drug development: are antiinflammatory drugs the next frontier?	2008 Sep 9	18779454
Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque.	2008 Sep 9	18765397
Phospholipase A2 inhibitors.	2009 Aug	19550325
Phospholipase A2 inhibitors in the treatment of atherosclerosis: a new approach moves forward in the clinic.	2009 Oct	19691442
Lipoprotein-associated phospholipase A(2) and atherosclerosis.	2009 Oct	19667981
Darapladib and atherosclerotic plaque: should lipoprotein-associated phospholipase A2 be a therapeutic target?	2009 Sep	19664375
Impact of medical therapy on atheroma volume measured by different cardiovascular imaging modalities.	2010	20672024
Darapladib: an emerging therapy for atherosclerosis.	2010 Aug	20660537
Phospholipase A2 inhibition and atherosclerotic vascular disease: prospects for targeting secretory and lipoprotein-associated phospholipase A2 enzymes.	2010 Dec	20739882
Darapladib.	2010 Jan	20001561
Trial watch: a boost for GSK's first-in-class heart drug?	2010 Jul	20592736
Editorial: why inhibition of lipoprotein-associated phospholipase A2 has the potential to improve patient outcomes.	2010 Jul	20485161
Association of carotid plaque Lp-PLA(2) with macrophages and Chlamydia pneumoniae infection among patients at risk for stroke.	2010 Jun 9	20543948
Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies.	2010 May 1	20435228
Study design and rationale for the clinical outcomes of the STABILITY Trial (STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY) comparing darapladib versus placebo in patients with coronary heart disease.	2010 Oct	20934559
Phospholipase A2s: developing drug targets for atherosclerosis.	2010 Oct	20363471

Patents

Sample Use Guides

In Vivo Use Guide

Single daily oral tablet

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

DARAPLADIB

Official Name

English

SB-480848

Code

English

Darapladib [WHO-DD]

Common Name

English

N-(2-(DIETHYLAMINO)ETHYL)-2-(2-(4-FLUOROBENZYLSULPHANYL)-4-OXO-4,5,6,7-TETRAHYDROCYCLOPENTAPYRIMIDIN-1-YL)-N-(4'-TRIFLUOROMETHYLBIPHENYL-4-YLMETHYL)ACETAMIDE

Systematic Name

English

DARAPLADIB [USAN]

Common Name

English

1H-CYCLOPENTAPYRIMIDINE-1-ACETAMIDE, N-(2-(DIETHYLAMINO)ETHYL)-2-(((4-FLUOROPHENYL)METHYL)THIO)-4,5,6,7-TETRAHYDRO-4-OXO-N-((4'-(TRIFLUOROMETHYL)(1,1'-BIPHENYL)-4-YL)METHYL)-

Systematic Name

English

DARAPLADIB [MI]

Common Name

English

darapladib [INN]

Common Name

English

DARAPLADIB [JAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29703