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

  • Bioorg Med Chem. 2009 Jan 1;17(1):411-7. doi: 10.1016/j.bmc.2007.12.040.
Vincent J Huber  1 ,  Mika Tsujita ,  Tsutomu Nakada
Affiliations
  • 1. Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Chuo-ku, 1 Asahi Machi Dori, Niigata 951-8585, Japan.
PMID: 18182301 DOI: 10.1016/j.bmc.2007.12.040
Abstract

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-HT(1B/1D) agonists sumatriptan, and rizatriptan. Moreover, the observed inhibitory activity of the compounds used in this study at 20 microM showed a strong correlation with their in silico docking energies, r(2)=0.64, which was consistent with that found in previous studies. The AQP4 inhibitory IC(50) values of three compounds, 2-(nicotinamido)-1,3,4-thiadiazole, sumatriptan and rizatriptan, were subsequently found to be 3, 11, and 2 microM, respectively.

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