title: Recent advances in the search for novel 5-lipoxygenase inhibitors.
abstract: 5-Lipoxygenase (5-LO) is an important enzyme of the arachidonic acid cascade and catalyses with the help of FLAP, the 5-LO-activating protein, the formation of bioactive leukotrienes (LTs). LTs are inflammatory mediators playing a pathophysiological role in different diseases such as asthma, allergic rhinitis as well as cardiovascular diseases and certain types of cancer. Up to now, only one 5-LO inhibitor is on the market, zileuton for the treatment of asthma. With the rising number of indications for anti-LT therapy, 5-LO inhibitor drug development becomes more and more important. This MiniReview gives an update on 5-LO inhibitors currently under clinical development. Furthermore, the recent advances in the search for novel 5-lipoxygenase inhibitors with a focus on computational methods are summarized. Currently, licofelone is the compound with the highest clinical development status (completed phase III trials). 5-LO inhibitor screening programmes based on computational methods could deliver several promising drug-like new molecules. These activities can be expected to be driven by the newly resolved structure of human 5-LO in the future, enabling structure-based drug design. For the prospective drugs in late-stage clinical development, the future will show their clinical safety and efficacy in the particular diseases.
authors: Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt, Germany.
authors: Dieter
authors: D
authors: Steinhilber
authors: Bettina
authors: B
authors: Hofmann
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D019295:Computational Biology; D015195:Drug Design; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy
chemical_list: D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011758:Pyrroles; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; C088092:licofelone