Dalcetrapib
CETP is shown to directly drive formation of cholesterol-rich remnant lipoprotein particles, and JTT-705 blocks the effect (Clin Chim Acta 2007)
Original title: Cholesteryl ester transfer protein promotes the formation of cholesterol-rich remnant like lipoprotein particles in human plasma
Although CETP was suspected to influence cholesterol levels in remnant-like lipoprotein particles (RLP), direct evidence was lacking. Researchers incubated human plasma with or without HDL containing tritium-labeled cholesteryl ester, recombinant CETP, or CETP inhibitors. RLP-cholesterol rose over time, and the increase correlated with plasma triglyceride level (r = 0.597, p = 0.0070) and with the amount of labeled cholesteryl ester transferred from HDL to the RLP fraction (r = 0.611, p = 0.0156). Recombinant CETP enhanced the RLP-cholesterol increase, while the CETP inhibitor JTT-705 (dalcetrapib) and an anti-CETP monoclonal antibody blocked both the RLP-cholesterol increase and the cholesteryl ester transfer, whereas inhibiting lecithin-cholesterol acyltransferase had no effect. JTT-705 also inhibited cholesteryl ester transfer to the RLP fraction more strongly than to non-RLP fractions, confirming that CETP drives cholesterol-rich RLP formation.
Original abstract
Background: Cholesteryl ester transfer protein (CETP) is suggested to be involved in the cholesterol level in remnant like lipoprotein particles (RLP), but there is no direct evidence that CETP increases cholesterol-rich RLP in plasma.
Methods: Human plasma was incubated with or without HDL containing [(3)H]-labeled cholesteryl ester ([(3)H]CE), recombinant CETP or CETP inhibitors at 37 degrees C in vitro.
Results: The RLP-cholesterol (RLP-C) level increased time-dependently and the amount of RLP-C increase (DeltaRLP-C) by the incubation was positively correlated with triglyceride (TG) level in plasma (r=0.597, P=0.0070). [(3)H]CE in HDL was transferred to RLP fraction under 37 degrees C incubation, and the amount of [(3)H]CE transferred to RLP correlated significantly with DeltaRLP-C in plasma (r=0.611, P=0.0156). Human recombinant CETP enhanced the RLP-C increase, while CETP inhibitor JTT-705 and anti-human CETP monoclonal antibody inhibited both the RLP-C increase and [(3)H]CE transfer to RLP. On the other hand, an inhibition of lecithin: cholesterol acyltransferase (LCAT) did not affect the RLP-C increase. In triglyceride-rich lipoproteins (TRL) fraction, JTT-705 inhibited [(3)H]CE transfer to RLP more strongly than that to non-RLP.
Conclusions: CETP promotes the formation of cholesterol-rich RLP through the transfer of CE from HDL to TRL and CETP inhibitors are useful to reduce RLP-C.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.