title: Inhibitors of phospholipase A2and their therapeutic potential: an update on patents (2012-2016).
abstract: The regulation of the catalytic activity of the various phospholipase A2enzymes is of high importance because these enzymes are involved in various pathological conditions such as arthritis, cardiovascular diseases, neurological diseases, and cancer. Thus, a great effort has been devoted in developing synthetic inhibitors as new agents to treat inflammatory diseases. Some of them have reached clinical trials. Areas covered: This review article discusses the phospholipase A2inhibitors presented in patent literature from October 2012 to June 2016, their activities in vitro and in vivo as well as the results of clinical trials using synthetic PLA2inhibitors. Expert opinion: None of the inhibitors studied in clinical trials have reached the market yet. The failure of lipoprotein-associated PLA2inhibitor darapladib to reduce the risk of major coronary events suggests that this enzyme may be a biomarker of vascular inflammation rather than a causal pathway of cardiovascular diseases. These findings, together with the failure of secreted PLA2inhibitor varespladib for the treatment of cardiovascular disease, indicate that deeper knowledge on these enzymes is needed. Inhibitors of cytosolic PLA2are in clinical trials against psoriasis and atopic dermatitis.
authors.affiliation: a Department of Chemistry , National and Kapodistrian University of Athens , Athens , Greece.
authors.forename: Maroula G
authors.initials: MG
authors.lastname: Kokotou
authors.affiliation: a Department of Chemistry , National and Kapodistrian University of Athens , Athens , Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Limnios
authors.affiliation: a Department of Chemistry , National and Kapodistrian University of Athens , Athens , Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Nikolaou
authors.affiliation: a Department of Chemistry , National and Kapodistrian University of Athens , Athens , Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Psarra
authors.affiliation: a Department of Chemistry , National and Kapodistrian University of Athens , Athens , Greece.
authors.forename: George
authors.initials: G
authors.lastname: Kokotos
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000473:pathology; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D007651:Keto Acids; D010091:Oximes / Q000494:pharmacology; D010330:Patents as Topic; D064801:Phospholipase A2 Inhibitors / Q000494:pharmacology*; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides
chemical_list: D000085:Acetates; D001547:Benzaldehydes; D015415:Biomarkers; D007211:Indoles; D007651:Keto Acids; D010091:Oximes; D064801:Phospholipase A2 Inhibitors; C117948:varespladib; C529040:darapladib; D001713:Biphenyl Compounds; D004048:Diethylamines; D011744:Pyrimidinones; D013440:Sulfides
keywords: Arthritis; atherosclerosis; autoimmune diseases; cancer; inflammation; inhibitors; phospholipase A2