Identification of Aquaporin 4 inhibitors using in vitro and in silico methods

The in vitro inhibitory effects and in silico docking energies of 18 compounds with respect to Aquaporin 4 (AQP4) were investigated. More than half of the compounds tested showed inhibitory activity in the in vitro functional assay and included the 5-HT1B/1D agonists sumatriptan, and rizatriptan. Moreover, the observed inhibitory activity of the compounds used in this study at 20 μM showed a strong correlation with their in silico docking energies, r2 = 0.64, which was consistent with that found in previous studies. The AQP4 inhibitory IC50 values of three compounds, 2-(nicotinamido)-1,3,4-thiadiazole, sumatriptan and rizatriptan, were subsequently found to be 3, 11, and 2 μM, respectively.

Eighteen compounds were studied for Aquaporin 4 inhibition using in vitro and in silico methods, of which 10 were found to clearly inhibit its water transport properties, P < 0.01, while another four showed weak but statistically significant inhibition, P < 0.05.Figure optionsDownload as PowerPoint slide