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=C(S)C=CC=C2
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)
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
Doses
| Dose | Population | Adverse events |
|---|---|---|
600 mg 1 times / day multiple, oral (unknown) Studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, ADULT n = 7938 Health Status: unhealthy Condition: acute coronary syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7938 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 (unknown) Highest studied dose Dose: 3900 mg, 1 times / day Route: oral Route: multiple Dose: 3900 mg, 1 times / day Sources: |
healthy n = 8 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 8 Sources: |
Other AEs: Flatulence, upper abdominal pai... Other AEs: Flatulence (25%) Sources: upper abdominal pai (38%) Nausea (13%) diarrhoea (75%) |
4500 mg single, oral (unknown) Highest studied dose |
healthy n = 11 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 11 Sources: |
Other AEs: diarrhoea, nausea... |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Diarrhea | 1.4% Disc. AE |
600 mg 1 times / day multiple, oral (unknown) Studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, ADULT n = 7938 Health Status: unhealthy Condition: acute coronary syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7938 Sources: |
| Hypertension | serious, 0.6% | 600 mg 1 times / day multiple, oral (unknown) Studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: |
unhealthy, ADULT n = 7938 Health Status: unhealthy Condition: acute coronary syndrome Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 7938 Sources: |
| Nausea | 13% | 3900 mg 1 times / day multiple, oral (unknown) Highest studied dose Dose: 3900 mg, 1 times / day Route: oral Route: multiple Dose: 3900 mg, 1 times / day Sources: |
healthy n = 8 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 8 Sources: |
| Flatulence | 25% | 3900 mg 1 times / day multiple, oral (unknown) Highest studied dose Dose: 3900 mg, 1 times / day Route: oral Route: multiple Dose: 3900 mg, 1 times / day Sources: |
healthy n = 8 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 8 Sources: |
| upper abdominal pai | 38% | 3900 mg 1 times / day multiple, oral (unknown) Highest studied dose Dose: 3900 mg, 1 times / day Route: oral Route: multiple Dose: 3900 mg, 1 times / day Sources: |
healthy n = 8 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 8 Sources: |
| diarrhoea | 75% | 3900 mg 1 times / day multiple, oral (unknown) Highest studied dose Dose: 3900 mg, 1 times / day Route: oral Route: multiple Dose: 3900 mg, 1 times / day Sources: |
healthy n = 8 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 8 Sources: |
| nausea | 18% | 4500 mg single, oral (unknown) Highest studied dose |
healthy n = 11 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 11 Sources: |
| diarrhoea | 45% | 4500 mg single, oral (unknown) Highest studied dose |
healthy n = 11 Health Status: healthy Sex: M Food Status: UNKNOWN Population Size: 11 Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| [CETP inhibitor]. | 2001 Mar |
|
| The Yin and Yang of cholesteryl ester transfer protein and atherosclerosis. | 2002 Dec |
|
| Cholesteryl ester transfer protein inhibitor (JTT-705) and the development of atherosclerosis in rabbits with severe hypercholesterolaemia. | 2002 Dec |
|
| Effect of HDL, from Japanese white rabbit administered a new cholesteryl ester transfer protein inhibitor JTT-705, on cholesteryl ester accumulation induced by acetylated low density lipoprotein in J774 macrophage. | 2002 May |
|
| Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. | 2002 May 7 |
|
| Effect of JTT-705 on cholesteryl ester transfer protein and plasma lipid levels in normolipidemic animals. | 2003 Apr 11 |
|
| Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. | 2003 Feb 1 |
|
| Dual effects on HDL metabolism by cholesteryl ester transfer protein inhibition in HepG2 cells. | 2003 Jun |
|
| JTT-705. Japan Tobacco. | 2004 Mar |
|
| Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. | 2006 Feb 7 |
|
| Therapeutic elevation of HDL-cholesterol to prevent atherosclerosis and coronary heart disease. | 2006 Sep |
|
| The role of CETP inhibition in dyslipidemia. | 2007 Aug |
|
| Inhibition of CETP as a novel therapeutic strategy for reducing the risk of atherosclerotic disease. | 2007 Jan |
|
| Cholesteryl ester transfer protein promotes the formation of cholesterol-rich remnant like lipoprotein particles in human plasma. | 2007 Jan |
|
| Cholesteryl ester transfer protein inhibition and HDL increase: has the dream ended? | 2008 Apr |
|
| Is raising HDL a futile strategy for atheroprotection? | 2008 Feb |
|
| Gateways to clinical trials. | 2008 May |
|
| HDL metabolism and CETP inhibition. | 2008 May-Jun |
|
| JTT-705: is there still future for a CETP inhibitor after torcetrapib? | 2008 Oct |
|
| Cholesterylestertransfer protein inhibition and endothelial function in type II hyperlipidemia. | 2009 |
|
| In vitro and in vivo assessment of the effect of dalcetrapib on a panel of CYP substrates. | 2009 Apr |
|
| Dalcetrapib: no off-target toxicity on blood pressure or on genes related to the renin-angiotensin-aldosterone system in rats. | 2009 Dec |
|
| The pharmacology and off-target effects of some cholesterol ester transfer protein inhibitors. | 2009 Nov 16 |
|
| Gateways to clinical trials. | 2009 Sep |
|
| Anacetrapib, a cholesterol ester transfer protein (CETP) inhibitor for the treatment of atherosclerosis. | 2009 Sep |
|
| MARCO, a macrophage scavenger receptor highly expressed in rodents, mediates dalcetrapib-induced uptake of lipids by rat and mouse macrophages. | 2010 Apr |
|
| 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 |
|
| Dalcetrapib: a review of Phase II data. | 2010 Jun |
|
| Biochemical characterization of cholesteryl ester transfer protein inhibitors. | 2010 Sep |
|
| Emerging drugs for hyperlipidemia. | 2010 Sep |
|
| Cholesteryl ester transfer protein inhibition in cardiovascular risk management: ongoing trials will end the confusion. | 2011 Dec |
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.
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211513-21-2
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6918816
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PEW5P6H57S
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DTXSID10426090
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PRODRUG (METABOLITE ACTIVE)
