Novel lipid-regulating drugs

Abstract

This review describes the major developments in lipid-regulating drugs during the past two years. Most of the novel compounds that have been launched or were in their final stages of development during this period are aimed primarily at lowering low-density lipoprotein (LDL)-cholesterol. These include bile acid sequestrants, HMG-CoA reductase inhibitors and a cholesterol absorption inhibitor. In addition, there have been preclinical reports suggesting the potential usefulness of orally bioavailable inhibitors of cholesterol ester transfer protein in plasma and of acylcoA:cholesterol acyltransferase in monocyte-macrophages. The recent discovery of the roles of the scavenger receptor class B Type 1 and ATP-binding cassette transporter 1 in high-density lipoprotein (HDL)-cholesterol transport may shift the trend of future developments away from compounds that lower LDL to those aimed at promoting HDL turnover.

HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis

“…22,[36][37][38][39] Statins derived from fungal fermentation include pravastatin, simvastatin, and lovastatin, whereas fluvastatin, atorvastatin, cerivastatin, rosuvastatin and pitavastatin are synthetic compounds. [40][41][42][43][44][45][46][47] The common structural characteristic of all statins is a side chain that exists either in a closed ring (inactive, lactone) or an open ring (active, acid) form ( Figure 2).…”

The Intestinal Absorption of Biliary and Dietary Cholesterol as a Drug Target for Lowering the Plasma Cholesterol Level

“…The importance of elevated plasma LDL‐C levels as a risk factor for CHD is apparent not only from epidemiologic studies, but also from the results of extensive clinical trials involving the use of lipid‐lowering drugs. Although several classes of cholesterol‐lowering agents are available, 4 the statins are currently the most widely used and the most effective treatment for hypercholesterolemia in the general population. Numerous trials have clearly demonstrated that statins, which are potent inhibitors of cholesterol biosynthesis, markedly lower plasma LDL‐C concentrations and bring about a commensurate reduction in the incidence of CHD events 5 .…”

“…It should be emphasized that ezetimibe belongs to an entirely new class of compounds that are structurally and mechanistically distinct from existing types of cholesterol‐lowering agents, including the bile acid binding resins that also act primarily at the level of the small intestine 4,31 . The resins are polymeric structures that bind bile acids in the intestinal lumen, thereby inhibiting their reabsorption and return to the liver 32 .…”

Exploitation of Bile Acid Transport Systems in Prodrug Design

“…Both primary and secondary conjugated and unconjugated bile acids are substrates for ASBT [2,72]. ASBT especially has been the target when designing drug delivery protocols, due to its unique substrate specificity and pivotal role in cholesterol homeostasis [80,81].…”