Aquaporin-4 as a therapeutic target: a first look

As one of the key mediators of cerebral water transport, aquaporin-4 (AQP4) has been widely considered a potential target for drug discovery. Many studies have shown a relationship between this protein and several diseases. However, efforts to identify AQP4 modulators that may be useful as therapeutics have been hindered by a lack of information on the types of molecular structures capable of binding to the protein, as well as the overall effect of such compounds. Recent studies, including the elucidation of the AQP4 solid-state structure, the identification of several classes of inhibitors and the combined weight of many biological studies, are beginning to clarify how to approach AQP4 from a drug discovery perspective. More specifically, sulfonamides, geminal diphenyl compounds and small heteroaromatics appear well suited for inhibiting AQP4, while ischemia, epilepsy and migraine have been proposed as indications for such molecules.