Insights into 5-LOX inhibitors binding modes, in order to help in the design of dual 5-LOX/COX-2 inhibitors

The arachidonic acid cascade is notably involved in various pathological processes such as inflammation and allergic disorders. It is comprised of two major metabolic pathways: the COX (with COX-1 and COX-2) and the 5-LOX ones. Simultaneous inhibition of 5-LOX and COX-2 appears to be a promising alternative to classical NSAIDs and even COX-2 inhibitors. Whereas COXs have already been extensively studied, current knowledge about 5-LOX is much more limited.
Therefore, this project aims the structural characterization of human 5-LOX and the study of its interaction with different selective inhibitors. Insights into pharmacophoric features, essential for an optimal inhibitory potency, will help in the design of new dual 5-LOX/COX-2 inhibitors.