Torcetrapib
Torcetrapib is a CETP inhibitor with IC50 of 37 nM, elevates HDL-C and reduces nonHDL-C in plasma. Inhibition of cholesteryl ester transfer protein (CETP) has been shown to have a substantial effect on plasma lipoprotein levels.
In vitro: Torcetrapib dose-dependently increases aldosterone release from H295R cells after either 24 or 48 h of treatment, this effect is mediated by calcium channel as calcium channel blockers completely blocks torcetrapib-induced corticoid release and calcium increase. Torcetrapib (1 μM) significantly increases the expression of steroidogenic gene, CYP11B2 and CYP11B1, in H295R cell lines [1].
In vivo: Researchers tested torcetrapib in rabbits fed an atherogenic diet at a dose sufficient to increase HDL-C by at least 3-fold. CETP activity was inhibited by 70–80% throughout the study. Non-HDL-C increased in both groups, but there was no difference apparent by the study’s end [2].
Clinical trial: Torcetrapib therapy resulted in an increased risk of mortality and morbidity of unknown
mechanism. Although there was evidence of an off-target effect of torcetrapib, adverse effects related to CETP inhibition cannot be ruled out [3].
References:
[1] Hu X, Dietz JD, Xia C, Knight DR, Loging WT, Smith AH, Yuan H, Perry DA, Keiser J. Torcetrapib induces aldosterone and cortisol production by an intracellular calcium-mediated mechanism independently of cholesteryl ester transfer protein inhibition. Endocrinology. 2009;150(5):2211-9.
[2] Morehouse LA, Sugarman ED, Bourassa PA, Sand TM, Zimetti F, Gao F, Rothblat GH, Milici AJ. Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits. J Lipid Res. 2007;48(6):1263-72.
[3] Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, Lopez-Sendon J, Mosca L, Tardif JC, Waters DD, Shear CL, Revkin JH, Buhr KA, Fisher MR, Tall AR, Brewer B; ILLUMINATE Investigators. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357(21):2109-22.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 600.47 |
| Cas No. | 262352-17-0 |
| Formula | C26H25F9N2O4 |
| Solubility | ≥22.4 mg/mL in DMSO; insoluble in H2O; ≥69 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | ethyl (2R,4S)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methoxycarbonylamino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2H-quinoline-1-carboxylate |
| SDF | Download SDF |
| Canonical SMILES | CCC1CC(C2=C(N1C(=O)OCC)C=CC(=C2)C(F)(F)F)N(CC3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)C(=O)OC |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Description | Torcetrapib is an inhibitor of cholesterylester transfer protein (CETP) with IC50 value of 50 nM. | |||||
| Targets | CETP | |||||
| IC50 | 50 nM | |||||
Quality Control & MSDS
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Chemical structure
