Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C19H29NOS |
| Molecular Weight | 319.505 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCC(CC)CC1(CCCCC1)C(=O)NC2=CC=CC=C2S
InChI
InChIKey=OVRLABAFXJPIMU-UHFFFAOYSA-N
InChI=1S/C19H29NOS/c1-3-15(4-2)14-19(12-8-5-9-13-19)18(21)20-16-10-6-7-11-17(16)22/h6-7,10-11,15,22H,3-5,8-9,12-14H2,1-2H3,(H,20,21)
| Molecular Formula | C19H29NOS |
| Molecular Weight | 319.505 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/20861162
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/20861162
Dalcetrapib (JTT-705) is a modulator than an inhibitor of cholesteryl ester transfer protein (CETP) activity and it may interact with and decrease CETP activity by a unique mechanism without an off-target effect. Dalcetrapib increased high-density lipoprotein (HDL) cholesterol levels but did not reduce the risk of cardiovascular events. It is in phase III of clinical trials for the treatment of acute coronary syndrome.
Originator
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
8.26 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21366361 |
4500 mg single, oral dose: 4500 mg route of administration: Oral experiment type: SINGLE co-administered: |
DALCETRAPIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
88.4 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21366361 |
4500 mg single, oral dose: 4500 mg route of administration: Oral experiment type: SINGLE co-administered: |
DALCETRAPIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
19.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21366361 |
4500 mg single, oral dose: 4500 mg route of administration: Oral experiment type: SINGLE co-administered: |
DALCETRAPIB plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
600 mg 1 times / day multiple, oral Studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Disc. AE: Diarrhea... Other AEs: Hypertension... AEs leading to discontinuation/dose reduction: Diarrhea (1.4%) Other AEs:Hypertension (serious, 0.6%) Sources: |
3900 mg 1 times / day multiple, oral Highest studied dose Dose: 3900 mg, 1 times / day Route: oral Route: multiple Dose: 3900 mg, 1 times / day Sources: |
healthy |
Other AEs: diarrhoea, Nausea... Other AEs: diarrhoea (75%) Sources: Nausea (13%) upper abdominal pai (38%) Flatulence (25%) |
4500 mg single, oral Highest studied dose |
healthy |
Other AEs: diarrhoea, nausea... |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Diarrhea | 1.4% Disc. AE |
600 mg 1 times / day multiple, oral Studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Hypertension | serious, 0.6% | 600 mg 1 times / day multiple, oral Studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
| Nausea | 13% | 3900 mg 1 times / day multiple, oral Highest studied dose Dose: 3900 mg, 1 times / day Route: oral Route: multiple Dose: 3900 mg, 1 times / day Sources: |
healthy |
| Flatulence | 25% | 3900 mg 1 times / day multiple, oral Highest studied dose Dose: 3900 mg, 1 times / day Route: oral Route: multiple Dose: 3900 mg, 1 times / day Sources: |
healthy |
| upper abdominal pai | 38% | 3900 mg 1 times / day multiple, oral Highest studied dose Dose: 3900 mg, 1 times / day Route: oral Route: multiple Dose: 3900 mg, 1 times / day Sources: |
healthy |
| diarrhoea | 75% | 3900 mg 1 times / day multiple, oral Highest studied dose Dose: 3900 mg, 1 times / day Route: oral Route: multiple Dose: 3900 mg, 1 times / day Sources: |
healthy |
| nausea | 18% | 4500 mg single, oral Highest studied dose |
healthy |
| diarrhoea | 45% | 4500 mg single, oral Highest studied dose |
healthy |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Monitoring Cyp2b10 mRNA expression at cessation of 2-year carcinogenesis bioassay in mouse liver provides evidence for a carcinogenic mechanism devoid of human relevance: the dalcetrapib experience. | 2012-03-15 |
|
| Cholesteryl ester transfer protein inhibition in cardiovascular risk management: ongoing trials will end the confusion. | 2011-12 |
|
| Lack of clinically relevant drug-drug interactions when dalcetrapib is co-administered with ezetimibe. | 2010-12 |
|
| Modulating cholesteryl ester transfer protein activity maintains efficient pre-β-HDL formation and increases reverse cholesterol transport. | 2010-12 |
|
| Good news for 'good' cholesterol. | 2010-11-18 |
|
| Low high-density lipoprotein cholesterol: current status and future strategies for management. | 2010-10-29 |
|
| No clinically relevant drug-drug interactions when dalcetrapib is co-administered with atorvastatin. | 2010-10 |
|
| Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin: no clinically relevant drug-drug interactions. | 2010-10 |
|
| Biochemical characterization of cholesteryl ester transfer protein inhibitors. | 2010-09 |
|
| Emerging drugs for hyperlipidemia. | 2010-09 |
|
| Update on CETP inhibition. | 2010-08-02 |
|
| Is a blood pressure rise the only deleterious off-target effect of cholesterol ester transfer protein inhibitors? | 2010-08 |
|
| Lack of effect of dalcetrapib on QT interval in healthy subjects following multiple dosing. | 2010-08 |
|
| Mechanisms underlying off-target effects of the cholesteryl ester transfer protein inhibitor torcetrapib involve L-type calcium channels. | 2010-08 |
|
| Dissociating HDL cholesterol from cardiovascular risk. | 2010-07-31 |
|
| Insights from recent meta-analysis: role of high-density lipoprotein cholesterol in reducing cardiovascular events and rates of atherosclerotic disease progression. | 2010-07-26 |
|
| High density lipoproteins-based therapies for cardiovascular disease. | 2010-07 |
|
| Dalcetrapib: a review of Phase II data. | 2010-06 |
|
| High-density lipoprotein-mediated anti-atherosclerotic and endothelial-protective effects: a potential novel therapeutic target in cardiovascular disease. | 2010-05 |
|
| MARCO, a macrophage scavenger receptor highly expressed in rodents, mediates dalcetrapib-induced uptake of lipids by rat and mouse macrophages. | 2010-04 |
|
| Mulling over the odds of CETP inhibition. | 2010-02 |
|
| Safety and tolerability of dalcetrapib (RO4607381/JTT-705): results from a 48-week trial. | 2010-02 |
|
| Functional assessment of HDL: Moving beyond static measures for risk assessment. | 2010-02 |
|
| [HDL and CETP in atherogenesis]. | 2010-02 |
|
| Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors. | 2010-01 |
|
| Dalcetrapib: JTT 705; JTT-705; R 1658; R1658; RG1658; RO 4607381; RO4607381. | 2010 |
|
| Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome. | 2009-12 |
|
| Dalcetrapib: no off-target toxicity on blood pressure or on genes related to the renin-angiotensin-aldosterone system in rats. | 2009-12 |
|
| The pharmacology and off-target effects of some cholesterol ester transfer protein inhibitors. | 2009-11-16 |
|
| Mechanism of inhibition defines CETP activity: a mathematical model for CETP in vitro. | 2009-11 |
|
| Gateways to clinical trials. | 2009-09 |
|
| Anacetrapib, a cholesterol ester transfer protein (CETP) inhibitor for the treatment of atherosclerosis. | 2009-09 |
|
| Cholesteryl ester transfer protein inhibitors as high-density lipoprotein raising agents. | 2009-09 |
|
| Free thiol group of MD-2 as the target for inhibition of the lipopolysaccharide-induced cell activation. | 2009-07-17 |
|
| Safety and tolerability of dalcetrapib. | 2009-07-01 |
|
| The end of the road for CETP inhibitors after torcetrapib? | 2009-07 |
|
| In vitro and in vivo assessment of the effect of dalcetrapib on a panel of CYP substrates. | 2009-04 |
|
| A single-center, open-label, one-sequence study of dalcetrapib coadministered with ketoconazole, and an in vitro study of the S-methyl metabolite of dalcetrapib. | 2009-03 |
|
| Cholesterylestertransfer protein inhibition and endothelial function in type II hyperlipidemia. | 2009 |
|
| Gateways to clinical trials. July-August 2008. | 2008-10-14 |
|
| JTT-705: is there still future for a CETP inhibitor after torcetrapib? | 2008-10 |
|
| Gateways to clinical trials. | 2008-05 |
|
| HDL metabolism and CETP inhibition. | 2008-04-17 |
|
| Cholesteryl ester transfer protein inhibition and HDL increase: has the dream ended? | 2008-04 |
|
| Is raising HDL a futile strategy for atheroprotection? | 2008-02 |
|
| The role of CETP inhibition in dyslipidemia. | 2007-08 |
|
| Inhibition of CETP as a novel therapeutic strategy for reducing the risk of atherosclerotic disease. | 2007-01 |
|
| Cholesteryl ester transfer protein promotes the formation of cholesterol-rich remnant like lipoprotein particles in human plasma. | 2007-01 |
|
| Are human CETP mutations and CETP-inhibiting drugs a good or a bad deal? | 2006-08 |
|
| Cholesteryl ester transfer protein inhibition, high-density lipoprotein metabolism and heart disease risk reduction. | 2006-08 |
Patents
Sample Use Guides
Human liver microsomes and a panel of substrates for CYP enzymes were used to determine IC(50) for inhibition of CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 by dalcetrapib. Drug was inhibitory to all CYP enzymes tested. IC(50) values ranged from 1.5 +/- 0.1 uM for CYP2C8 to 82 +/- 4 uM for CYP2D6.
| Substance Class |
Chemical
Created
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