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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 of DARAPLADIB

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
Molecular Formula C36H38F4N4O2S
Molecular Weight 666.771
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 0.25 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
656
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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

Sourcing

Vendor/AggregatorIDURL
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

PubMed

TitleDatePubMed
The identification of clinical candidate SB-480848: a potent inhibitor of lipoprotein-associated phospholipase A2.
2003 Mar 24
Gateways to clinical trials.
2006 Sep
Gateways to clinical trials.
2008 Apr
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
Gateways to clinical trials. July-August 2008.
2008 Jul-Aug
Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development.
2008 Oct
Inhibition of lipoprotein-associated phospholipase activity by darapladib: shifting gears in cardiovascular drug development: are antiinflammatory drugs the next frontier?
2008 Sep 9
Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque.
2008 Sep 9
Low and high density lipoprotein--cholesterol and coronary atherothrombosis.
2009
Update on patented cholesterol absorption inhibitors.
2009 Aug
Phospholipase A2 inhibitors.
2009 Aug
Phospholipase A2 inhibitors in atherosclerosis: the race is on.
2009 Feb 21
Lipoprotein-associated phospholipase A2 as a biomarker of coronary heart disease and a therapeutic target.
2009 Jul
Darapladib, a reversible lipoprotein-associated phospholipase A2 inhibitor, for the oral treatment of atherosclerosis and coronary artery disease.
2009 Oct
Phospholipase A2 inhibitors in the treatment of atherosclerosis: a new approach moves forward in the clinic.
2009 Oct
Lipoprotein-associated phospholipase A(2) and atherosclerosis.
2009 Oct
Darapladib and atherosclerotic plaque: should lipoprotein-associated phospholipase A2 be a therapeutic target?
2009 Sep
Impact of medical therapy on atheroma volume measured by different cardiovascular imaging modalities.
2010
A new method to measure necrotic core and calcium content in coronary plaques using intravascular ultrasound radiofrequency-based analysis.
2010 Apr
Darapladib: an emerging therapy for atherosclerosis.
2010 Aug
Phospholipase A2 inhibition and atherosclerotic vascular disease: prospects for targeting secretory and lipoprotein-associated phospholipase A2 enzymes.
2010 Dec
Lp-PLA2: A new target for statin therapy.
2010 Jan
Darapladib.
2010 Jan
Trial watch: a boost for GSK's first-in-class heart drug?
2010 Jul
Editorial: why inhibition of lipoprotein-associated phospholipase A2 has the potential to improve patient outcomes.
2010 Jul
Impact of analyzing less image frames per segment for radiofrequency-based volumetric intravascular ultrasound measurements in mild-to-moderate coronary atherosclerosis.
2010 Jun
Extracellular phospholipases in atherosclerosis.
2010 Jun
Association of carotid plaque Lp-PLA(2) with macrophages and Chlamydia pneumoniae infection among patients at risk for stroke.
2010 Jun 9
Lipoprotein-associated phospholipase A2: a new therapeutic target.
2010 Mar
Lipoprotein-associated phospholipase A2: role in atherosclerosis and utility as a cardiovascular biomarker.
2010 Mar
Lipoprotein-associated phospholipase A2 activity and incident coronary heart disease among men and women with type 2 diabetes.
2010 May
Lipoprotein-associated phospholipase A(2) and risk of coronary disease, stroke, and mortality: collaborative analysis of 32 prospective studies.
2010 May 1
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
Phospholipase A2s: developing drug targets for atherosclerosis.
2010 Oct
Patents

Patents

WO2015114479 A1
1

Sample Use Guides

In Vivo Use Guide
Single daily oral tablet
Route of Administration: Oral
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Sat Dec 16 15:51:33 GMT 2023
Edited
by admin
on Sat Dec 16 15:51:33 GMT 2023
Record UNII
UI1U1MYH09
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DARAPLADIB
INN   MI   USAN   WHO-DD  
USAN   INN  
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
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
Code System Code Type Description
FDA UNII
UI1U1MYH09
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
EVMPD
SUB32277
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
MESH
C529040
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
CAS
356057-34-6
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
INN
8703
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
MERCK INDEX
m4094
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY Merck Index
WIKIPEDIA
Darapladib
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
USAN
RR-57
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
SMS_ID
100000124361
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
ChEMBL
CHEMBL204021
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
PUBCHEM
9939609
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
NCI_THESAURUS
C72985
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
EPA CompTox
DTXSID70189073
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
DRUG BANK
DB06311
Created by admin on Sat Dec 16 15:51:33 GMT 2023 , Edited by admin on Sat Dec 16 15:51:33 GMT 2023
PRIMARY
Related Record Type Details
PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE
TARGET -> INHIBITOR
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TARGET ORGANISM->INHIBITOR
Related Record Type Details
Structure of DARAPLADIB
ACTIVE MOIETY
NIH
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