New Idol for cholesterol reduction?

The discovery of the statins was a great success in cardiovascular research and pharmaceuticals development. It was the answer to the epidemiologic problem that higher plasma cholesterol concentrations were associated with a higher occurrence of coronary artery disease (CAD) events. The statins inhibit a ratelimiting enzyme of cholesterol synthesis, hydroxymethylglutaryl (HMG)-CoA reductase, and consequently reduce the plasma LDL cholesterol concentration. Clinical trials proved the lower the better law for cholesterol as long as statins are used. This success pushed various kinds of cholesterol-reducing agents into the pipelines of pharmaceutical companies. Those cholesterol-reducing drugs that followed statins were cholesteryl ester transporter protein (CETP) inhibitors, Niemann–Pick C1-like 1 (NPC1L1) inhibitors, microsomal triglyceride transfer protein (MTTP) inhibitors, and acyl-CoA cholesterol acyltransferase (ACAT) inhibitors. These chemicals effectively reduced plasma LDL through different modes of action from statins. Agents that increase the number of LDL receptors (LDLRs) were once sought. One such agent, estrogen, while being an endogenous molecule, was shown to actually exhibit antiatherogenic effects in part by increasing LDLRs in liver and thus decreasing LDL in plasma. In the July 3, 2009, issue of Science, Zelcer et al. (1 ) reported to have found a new mechanism to regulate the number of LDLRs, which would be a drug target to control LDL. The molecule Idol (inducible degrader of LDLRs) that they found might be a molecular target for such a strategy. Intracellular Regulation of Cholesterol Level