Novel microsomal triglyceride transfer protein inhibitors

Abstract

Microsomal triglyceride transfer protein (MTP) mediates triglyceride absorption and chylomicron secretion from the intestine and very-low-density lipoprotein (VLDL) secretion from the liver, by linking lipid molecules with apolipoprotein B (ApoB). Inhibition of MTP reduces the level of all ApoB-containing lipoproteins, including low-density lipoprotein (LDL). High-throughput screening has produced several families of compounds that are effective in vitro and in vivo as MTP inhibitors and some drugs are currently at clinical trial stage. Drugs that inhibit MTP can potentially be very effective in reducing atherosclerotic vascular disease by lowering levels of all the atherogenic lipoproteins. Partial inhibition of MTP by an inhibitor could be particularly useful when combined with other drugs that alter lipid metabolism but marked inhibition of MTP could cause significant adverse effects.

• apolipoprotein B (ApoB)
• chylomicron
• microsomal triglyceride transfer protein (MTP)
• triglyceride
• very-low-density lipoprotein (VLDL)