U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C30H25F10NO3
Molecular Weight 637.5095
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ANACETRAPIB

SMILES

CC(C)c1cc(-c2ccc(cc2CN3[C@@]([H])(C)[C@@]([H])(c4cc(cc(c4)C(F)(F)F)C(F)(F)F)OC3=O)C(F)(F)F)c(cc1F)OC

InChI

InChIKey=MZZLGJHLQGUVPN-HAWMADMCSA-N
InChI=1S/C30H25F10NO3/c1-14(2)22-11-23(25(43-4)12-24(22)31)21-6-5-18(28(32,33)34)9-17(21)13-41-15(3)26(44-27(41)42)16-7-19(29(35,36)37)10-20(8-16)30(38,39)40/h5-12,14-15,26H,13H2,1-4H3/t15-,26-/m0/s1

HIDE SMILES / InChI

Molecular Formula C30H25F10NO3
Molecular Weight 637.5095
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: Description was created based on several sources, including http://www.selleckchem.com/products/anacetrapib-mk-0859.html

Anacetrapib is a CETP inhibitor being developed by Merck to treat hypercholesterolemia (elevated cholesterol levels) and prevent cardiovascular disease. Anacetrapib is a cholesterol ester transfer protein (CETP) inhibitor that blocks the transfer of cholesterol from highdensity lipoprotein to other lipoproteins. This results in an increase in high-density lipoprotein cholesterol (HDL-C) and a decrease in lowdensity lipoprotein cholesterol (LDL-C), which may reduce the development of atherosclerosis. Anacetrapib has not been approved for sale in Canada or the United States. Clinical evidence to support the use of anacetrapib for dyslipidemia has been reported in two clinical trials. REVEAL is an ongoing, large-scale phase 3 trial evaluating the effectiveness of anacetrapib with a statin for the secondary prevention of major coronary events in patients who have a history of cardiovascular disease. Results are anticipated in January 2017.

Originator

Curator's Comment:: # Merck & Co

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.45 μM
300 mg 1 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ANACETRAPIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4460 ng/mL
10 mg/kg single, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANACETRAPIB plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
9140 nM
800 mg 1 times / day single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANACETRAPIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
889 nM
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANACETRAPIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
34.95 μM × h
300 mg 1 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ANACETRAPIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
109000 ng × min/mL
10 mg/kg single, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANACETRAPIB plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
117.4 μM × h
800 mg 1 times / day single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANACETRAPIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
13.6 μM × h
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANACETRAPIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
371 min
10 mg/kg single, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANACETRAPIB plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
82.6 h
800 mg 1 times / day single, oral
dose: 800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANACETRAPIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
61.9 h
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANACETRAPIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
8.98%
10 mg/kg single, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
ANACETRAPIB plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1000 mg single, oral
Highest studied dose
Dose: 1000 mg
Route: oral
Route: single
Dose: 1000 mg
Sources: Page: p.544
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: FASTED
Population Size: 6
Sources: Page: p.544
300 mg 1 times / day multiple, oral (total daily dose)
Studied dose
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources: Page: p.57, 58
unhealthy, ADULT
n = 41
Health Status: unhealthy
Condition: dyslipidemia
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 41
Sources: Page: p.57, 58
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled phase I studies.
2007 Dec 8
Cholesteryl ester transfer protein inhibition and HDL increase: has the dream ended?
2008 Apr
Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone.
2008 Aug
The failure of torcetrapib: what have we learned?
2008 Aug
Multiple-dose pharmacodynamics and pharmacokinetics of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.
2008 Dec
Treating high-density lipoprotein cholesterol: a return to inhibition of cholesteryl ester transfer protein?
2008 Jun
Anacetrapib: new hope for cholesteryl ester transfer protein inhibitors in the treatment of dyslipidemia.
2008 Jun
Gateways to clinical trials.
2008 Mar
HDL metabolism and CETP inhibition.
2008 May-Jun
JTT-705: is there still future for a CETP inhibitor after torcetrapib?
2008 Oct
Gateways to clinical trials.
2009 Apr
Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib as monotherapy and coadministered with atorvastatin in dyslipidemic patients.
2009 Feb
Assessment of the CYP3A-mediated drug interaction potential of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy volunteers.
2009 Jan
Effect of cholesteryl ester transfer protein inhibitor on vitamin E transport should be studied.
2009 Jul
The end of the road for CETP inhibitors after torcetrapib?
2009 Jul
Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.
2009 May
Drug discovery using chemical systems biology: identification of the protein-ligand binding network to explain the side effects of CETP inhibitors.
2009 May
Triglycerides and HDL cholesterol: stars or second leads in diabetes?
2009 Nov
The pharmacology and off-target effects of some cholesterol ester transfer protein inhibitors.
2009 Nov 16
Single-dose pharmacokinetics and pharmacodynamics of anacetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.
2009 Oct
Design of the DEFINE trial: determining the EFficacy and tolerability of CETP INhibition with AnacEtrapib.
2009 Oct
High-density lipoprotein cholesterol: current perspective for clinicians.
2009 Oct-Nov
Anacetrapib, a cholesterol ester transfer protein (CETP) inhibitor for the treatment of atherosclerosis.
2009 Sep
Cholesteryl ester transfer protein inhibitors as high-density lipoprotein raising agents.
2009 Sep
Anacetrapib.
2010
Modulating cholesteryl ester transfer protein activity maintains efficient pre-β-HDL formation and increases reverse cholesterol transport.
2010 Dec
[HDL and CETP in atherogenesis].
2010 Feb
Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors.
2010 Jan
Gateways to clinical trials.
2010 Jan-Feb
Cholesterol efflux potential and antiinflammatory properties of high-density lipoprotein after treatment with niacin or anacetrapib.
2010 Jul
Dissociating HDL cholesterol from cardiovascular risk.
2010 Jul 31
[Recent advances in the research on HDL subfraction].
2010 Jun
Dalcetrapib: a review of Phase II data.
2010 Jun
Metabolism and excretion of anacetrapib, a novel inhibitor of the cholesteryl ester transfer protein, in humans.
2010 Mar
Pharmacokinetics, metabolism, and excretion of anacetrapib, a novel inhibitor of the cholesteryl ester transfer protein, in rats and rhesus monkeys.
2010 Mar
Current status and future directions in lipid management: emphasizing low-density lipoproteins, high-density lipoproteins, and triglycerides as targets for therapy.
2010 Mar 3
High-density lipoprotein-mediated anti-atherosclerotic and endothelial-protective effects: a potential novel therapeutic target in cardiovascular disease.
2010 May
Effects of fenofibrate on lipid profiles, cholesterol ester transfer activity, and in-stent intimal hyperplasia in patients after elective coronary stenting.
2010 Oct 25
Biochemical characterization of cholesteryl ester transfer protein inhibitors.
2010 Sep
Emerging drugs for hyperlipidemia.
2010 Sep
Drug off-target effects predicted using structural analysis in the context of a metabolic network model.
2010 Sep 23
Cholesteryl ester transfer protein inhibition in cardiovascular risk management: ongoing trials will end the confusion.
2011 Dec
Patents

Sample Use Guides

tablet, 100mg daily
Route of Administration: Oral
Anacetrapib (0.1 to 10 uM) dose-dependently inhibited pre-β-HDL formation in vitro in human plasma
Substance Class Chemical
Created
by admin
on Sat Jun 26 07:40:59 UTC 2021
Edited
by admin
on Sat Jun 26 07:40:59 UTC 2021
Record UNII
P7T269PR6S
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ANACETRAPIB
INN   MART.   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
MK0859
Code English
ANACETRAPIB [INN]
Common Name English
2-OXAZOLIDINONE, 5-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)-3-((4'-FLUORO-2'-METHOXY-5'-(1-METHYLETHYL)-4-(TRIFLUOROMETHYL)(1,1'-BIPHENYL)-2-YL)METHYL)-4-METHYL-, (4S,5R)-
Common Name English
ANACETRAPIB [USAN]
Common Name English
(4S,5R)-5-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)-3-((4'-FLUORO-2'-METHOXY-5'-(PROPAN-2-YL)-4-(TRIFLUOROMETHYL)(1,1'-BIPHENYL)-2-YL)METHYL)-4-METHYL-1,3-OXAZOLIDIN-2-ONE
Common Name English
ANACETRAPIB [WHO-DD]
Common Name English
ANACETRAPIB [MART.]
Common Name English
MK-0859
Code English
ANACETRAPIB [JAN]
Common Name English
ANACETRAPIB [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C471
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
NCI_THESAURUS C29703
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C75251
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
PRIMARY
EPA CompTox
875446-37-0
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
PRIMARY
EVMPD
SUB34824
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
PRIMARY
WIKIPEDIA
ANACETRAPIB
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
PRIMARY
MESH
C530884
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
PRIMARY
DRUG BANK
DB06630
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
PRIMARY
PUBCHEM
11556427
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
PRIMARY
INN
8926
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
PRIMARY
CAS
875446-37-0
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
PRIMARY
ChEMBL
CHEMBL1800807
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
PRIMARY
MERCK INDEX
M1885
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
PRIMARY Merck Index
FDA UNII
P7T269PR6S
Created by admin on Sat Jun 26 07:41:00 UTC 2021 , Edited by admin on Sat Jun 26 07:41:00 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TARGET -> INHIBITOR
SELECTIVE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION