MTP

Cholesteryl Ester Transfer Protein (CETP) is a hydrophobic glycoprotein secreted mainly from the liver and circulates in plasma, bound mainly to HDL. It reduces circulating HDL cholesterol levels by promoting the transfer of cholesteryl esters from antiatherogenic HDLs to proatherogenic apolipoprotein B (apoB)–containing lipoproteins, including VLDLs, VLDL remnants, IDLs, and LDLs in exchange for triglyceride[1]. Its activity is associated with conditions linked with accelerated atherosclerosis including diabetes, metabolic syndrome and the dyslipidaemia typically found in myocardial infarction survivors.  CETP is a member of a family of proteins expressed in species including man and rabbit, which are susceptible to atherosclerosis, but not in rats, which are resistant to atherogenesis[2]. Dalcetrapib and Torcetrapib (Axon 1962 and Axon 2047 respectively) both inhibit CETP activity, resulting in increased levels of HDL cholesterol, and decreased levels of LDL cholesterol. However, in case of Torcetrapib, not Dalcetrapib[3], the beneficial pharmacological effects are accompanied by an increased risk of cardiovascular events leading to mortality and morbidity[4].
The microsomal triglyceride transfer protein (MTP) plays a crucial role in the assembly of triglycerides (TG), cholesterol esters, and phospholipids into ApoB-containing lipoproteins and is integral in the assembly of very low-density lipoprotein-cholesterol (VLDL-C) in the liver. As a result, inhibition of hepatic MTP could be a promising alternative strategy for the control of circulating levels of LDL-C and TG[5].


[1] P.J. Barter et al. Cholesteryl Ester Transfer Protein. A Novel Target for RaisingHDL and Inhibiting Atherosclerosis. Arteriosc. Thromb. Vasc. Biol. 2003, 23, 160-167.
[2] P.N. Durrington. Cholesteryl Ester Transfer Protein (CETP) Inhibitors. Br. J. Cardiol. 2012, 19, 126-133.
[3] T.F. Lüscher et al. 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. 2012, 33, 857-865.
[4] P.J. Barter et al. Effects of torcetrapib in patients at high risk for coronary events. N. Engl. J. Med. 2007, 357, 2109-2122.
[5] E. Kim  et al. A small-molecule inhibitor of enterocytic microsomal triglyceride transfer protein, SLx-4090: biochemical, pharmacodynamic, pharmacokinetic, and safety profile. J. Pharmacol. Exp. Ther. 2011, 337, 775-785.

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Axon ID Name Description From price
2216 CP 346086 Potent microsomal triglyceride transfer protein (MTP) inhibitor €125.00

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