Dalcetrapib
| Dalcetrapib | |
|---|---|
 | |
| IUPAC name S-[2-({[1-(2-ethylbutyl)cyclohexyl]carbonyl}amino)phenyl] 2-methylpropanethioate | |
| Identifiers | |
| CAS number | 211513-37-0 |
| PubChem | 6918540 |
| ChemSpider | 5293737 |
| ChEMBL | CHEMBL313006 |
| Jmol-3D images | Image 1 |
| |
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| Properties | |
| Molecular formula | C23H35NO2S |
| Molar mass | 389.5945 |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa) | |
| Infobox references | |
Dalcetrapib or JTT-705 is a CETP inhibitor which was being developed by Hoffmann–La Roche until May 2012.[1][2] The drug was aimed at raising the blood levels of "good cholesterol" (cholesterol carried in HDL particles, aka HDL-C).[3] Prevailing observations indicate that high HDL levels correlate with better overall cardiovascular health, though it remains unclear whether raising HDL levels consequently leads to an increase in cardiovascular health.[4]
A 24 week clinical trial showed that dalcetrapib did increase HDL-C levels, supporting the agent's desired effect.[5] Further, the dal-PLAQUE phase IIb trial found evidence of plaque reduction.[6] Plaque reduction is an anticipated observation following an increase in HDL.[citation needed]
As of 2010 five phase II trials had started and there was no evidence of the raised blood pressure seen with torcetrapib.[5]
dal-VESSEL phase IIb trial found no evidence of flow-mediated dilatation improvement. A 17% increase of Lp-PLA2 mass level was noted.[7] Lp-PLA2 is associated with coronary heart disease and stroke.[citation needed]
dal-OUTCOMES phase III trial passed its first interim review in July, 2011,[8] however, development was halted on May 7, 2012 “due to a lack of clinically meaningful efficacy.”.[2]
The results of dal-OUTCOMES III were published in November, 2012.[9]
See also
- CETP inhibitor, which contains links to related agents; as of November 2012: Torcetrapib, Anacetrapib, Dalcetrapib and Evacetrapib
References
- ↑ Huang Z, Inazu A, Nohara A, Higashikata T, Mabuchi H (December 2002). "Cholesteryl ester transfer protein inhibitor (JTT-705) and the development of atherosclerosis in rabbits with severe hypercholesterolaemia". Clin. Sci. 103 (6): 587–594. PMID 12444911.
- ↑ 2.0 2.1 Simeon Bennett and Naomi Kresge. "Roche Drops After Halting Cholesterol Drug Development".
- ↑ Michelle Fay Cortez (November 5, 2012), "Roche’s Good Cholesterol Drug Shows Negative Side Effects", Bloomberg Businessweek, retrieved November 6, 2012
- ↑ "NIH stops clinical trial on combination cholesterol treatment". National Institute of Health. NHLBI. Retrieved June 2, 2011.
- ↑ 5.0 5.1 Stein et al. (2010). "Safety and tolerability of dalcetrapib (RO4607381/JTT-705): results from a 48-week trial". Eur. Heart J. 31 (4): 480–4888. doi:10.1093/eurheartj/ehp601. PMC 2821630. PMID 20097702. Unknown parameter
|unused_data=ignored (help) - ↑ Zahi A Fayad et al. (2011). "Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial". The Lancet 378 (9802): 1547–1559. doi:10.1016/S0140-6736(11)61383-4.
- ↑ Thomas F. Lüscher et al. (2012). "Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease: the dal-VESSEL randomized clinical trial". Eur. Heart J. doi:10.1093/eurheartj/ehs019.
- ↑ Gail Parziale. "Dalcetrapib and Anacetrapib: a Tale of Two CETPs".
- ↑ Schwartz, G. G.; Olsson, A. G.; Abt, M.; Ballantyne, C. M.; Barter, P. J.; Brumm, J.; Chaitman, B. R.; Holme, I. M.; Kallend, D.; Leiter, L. A.; Leitersdorf, E.; McMurray, J. J. V.; Mundl, H.; Nicholls, S. J.; Shah, P. K.; Tardif, J. C.; Wright, R. S.; Dal-Outcomes, I. (2012). "Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome". New England Journal of Medicine 367 (22): 2089–2099. doi:10.1056/NEJMoa1206797. PMID 23126252.
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