darapladib and succinobucol

How to manage residual atherosclerosis risk after the statin therapy is a major concern in cardiovascular medicine. In addition to life-style modifications, new drugs against atherosclerotic and inflammatory vascular diseases are expected. In current clinical trials, phospholipase A2 inhibitors(darapladib, varespladib), RVX-208, D-4F, CETP inhibitors (anacetrapib, dalcetrapib), succinobucol are investigated. Some has been failed, but others are still promising. On molecular target basis of PAF-AH, CETP, PON, ABC transporters of A1 and G1, SR-BI, HO-1, potential benefits and side effects are discussed.

Topics: Acetates; Amides; Apolipoprotein A-I; Atherosclerosis; Benzaldehydes; Blood Proteins; Cholesterol Ester Transfer Proteins; Clinical Trials as Topic; Drug Design; Esters; Humans; Indoles; Keto Acids; Molecular Targeted Therapy; Oxazolidinones; Oximes; Probucol; Quinazolines; Quinazolinones; Sulfhydryl Compounds

Cardiovascular diseases remain a major cause of morbidity and mortality worldwide, regardless of the recent advances in medical and surgical treatment, for as life expectancy in the developed countries increases, cardiovascular conditions affecting the elderly also rises. Atherosclerosis and cardiovascular diseases take a huge toll on the society, making them the leading cause of death in developed countries. Phenomenal advances in the pathophysiology of cardiovascular disease and the molecular signaling pathways has revealed the role of endothelial dysfunction involved therein and thus has raised the possibility of novel therapeutic targets. Such potential cellular targets include the vascular smooth muscle cells, monocyte/macrophage cell lines, platelets, and endothelial cells. Certain studies affirm that antiplatelet agents, antioxidant therapies, amino acid supplementation, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers may prevent or slow the progression of the disease process. The race is on for new medicines that can treat and prevent heart attacks and strokes, arising out of atherosclerosis, which kills nearly 1 million people a year in the U.S.A alone.

Topics: Anticholesteremic Agents; Benzaldehydes; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Endothelin Receptor Antagonists; Fibrinolytic Agents; Humans; Immunologic Factors; Isoxazoles; Lipoxygenase Inhibitors; Metalloendopeptidases; Oxazolidinones; Oximes; Phospholipase A2 Inhibitors; Probucol; Pyrimidines; Quinolines; Thiophenes