Dalcetrapib
JTT-705 (dalcetrapib) inhibits CETP and raises HDL-C across five animal species, mimicking CETP-deficient humans in marmosets (Eur J Pharmacol 2003)
Original title: Effect of JTT-705 on cholesteryl ester transfer protein and plasma lipid levels in normolipidemic animals
Researchers characterized JTT-705, later named dalcetrapib, as a CETP inhibitor across species. In vitro, JTT-705 inhibited plasma CETP activity in humans, rabbits, hamsters, cynomolgus monkeys, and marmosets with IC50 values of 5.5, 1.0, 11.7, 2.4, and 6.3 uM, respectively, while its thiol metabolite JTP-25203 was more potent (IC50 2.8, 0.44, 0.52, 1.3, and 1.1 uM). Given orally to normolipidemic rabbits, hamsters, and marmosets, JTT-705 reduced plasma CETP activity, raised HDL cholesterol, and lowered the non-HDL/HDL cholesterol ratio in all three species, and in marmosets it increased apoE-rich HDL on agarose gel electrophoresis, resembling the HDL profile of CETP-deficient humans. The authors conclude JTT-705 can be expected to inhibit CETP activity and improve lipoprotein profiles broadly across species, including humans.
Original abstract
This study evaluated JTT-705, S-[2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl]2-methylpropanethioate, as a cholesteryl ester transfer protein (CETP) inhibitor in several animal species. In vitro, JTT-705 inhibited plasma CETP activities of humans, rabbits, hamsters, cynomolgus monkeys and marmosets with IC(50) values of 5.5, 1.0, 11.7, 2.4 and 6.3 microM, respectively. The thiol form (JTP-25203) also inhibited those activities with IC(50) values of 2.8, 0.44, 0.52, 1.3 and 1.1 microM, respectively. Following oral administration to normolipidemic animals (rabbits, hamsters and marmosets), JTT-705 reduced plasma CETP activity, increased high density lipoprotein cholesterol (HDL-cholesterol), and decreased the ratio of non-HDL-cholesterol to HDL-cholesterol (atherogenic index) in all species. In marmosets, JTT-705 increased slow alpha-migrating lipoprotein (apolipoprotein E-rich HDL) in agarose gel electrophoresis, indicating that HDL metabolism in JTT-705-treated marmosets is similar to that in CETP-deficient humans. These results indicate that JTT-705 can be expected to inhibit plasma CETP activity and improve plasma lipoprotein profiles in a wide range of animal species, including humans.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.