Phospholipase A2 inhibitors in the treatment of atherosclerosis: a new approach moves forward in the clinic.
Phase II results of the trials of two phospholipase A2 inhibitors which may be of value in the treatment of atherosclerosis and cardiovascular disease have been reported in the past year. Darapladib (GlaxoSmithKline) is an inhibitor of lipoprotein-associated phospholipase A2 and varespladib (Anthera) inhibits several forms of the secreted phospholipase A2s. Despite the apparent similarity of mechanism, which is also built into the compounds' names, the role of the two types of phospholipase in atherogenesis is very different. Evidence for this comes from a range of preclinical studies and from epidemiological data which are summarised here. These data provide a basis for the Phase II studies and support decisions to move into Phase III, a decision which in the case of darapladib has been made and studies commenced (STABILITY trial). For varespladib the FRANCIS-ACS trial in acute coronary syndrome patients is in progress.
Suckling
Keith E
KE
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000037:antagonists & inhibitors; D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D001547:Benzaldehydes / Q000494:pharmacology / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007651:Keto Acids; D010091:Oximes / Q000494:pharmacology / Q000627:therapeutic use; D064801:Phospholipase A2 Inhibitors; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000085:Acetates; D001547:Benzaldehydes; D004791:Enzyme Inhibitors; D007211:Indoles; D007651:Keto Acids; D010091:Oximes; D064801:Phospholipase A2 Inhibitors; C117948:varespladib; C529040:darapladib; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides