Roles for novel pharmacological blockers of aquaporins in the treatment of brain oedema and cancer

Summary 1. Aquaporins are targets for drug discovery for basic research and medicine. Human diseases involving fluid imbalances and oedema are of major concern, and involv et issues in which aquaporins are expressed. The range of functional properties of aquaporins is continuing to expand steadily with ongoing research in the field. 2. Gating domains in aquaporins (AQPs) are molecular sites for drug actions. Discovery of the arylsulfonamide AqB013 as an antagonist for AQP1 and AQP4 provided the first pharmacological agent with translational promise for the treatment of diseases in which AQPs ha ve b een implicated. The putative b inding site for AqB013 in the internal vestibule of the AQP water pore involves amino acid residues that are located in the A QP loop D gating domain. 3. Aquaporins have been proposed as nove lt argets in cancer and oedema, and are associated with a surprising array of important processes in the brain and body such as angiogenesis, cell migration, development, and neuropathological diseases. Functions beyond their simple role as water channels are suggested by the subtype-specific regulation of AQP expression. In both cancer and brain oedema, current therapies are limited, and ne w pharmacological approaches focused on AQPs offer exciting potential for clinical advances. Aquaporins ar et argets for drug discovery for basic research and medicine