Identification of arylsulfonamides as Aquaporin 4 inhibitors
Graphical abstract
A series of carbonic anhydrase inhibitors, including AZA, have been found to inhibit AQP4 mediated water transport in an in vitro functional assay. AZA has an apparent IC50 = 0.9 μM against human AQP4-M23.
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Acknowledgments
Support for this research was provided from the Ministry of Education, Culture, Sports, Science and Technology (Japan); Grant for the Promotion of University of Niigata Research Projects (University of Niigata, Center for Transdisciplinary Research); Takeda Science Foundation.
References and notes (31)
- et al.
J. Biol. Chem.
(1994) DDT
(2005)- et al.
J. Biol. Chem.
(2006) - et al.
Anal. Biochem.
(2006) - et al.
Neurosci. Lett.
(1994) - et al.
J. Biol. Chem.
(2001) - et al.
J. Mol. Biol.
(2006) - et al.
FEBS Lett.
(1990) - et al.
Bioorg. Med. Chem. Lett.
(2005) Proc. Am. Thor. Soc.
(2006)
Gen. Bio.
Proc. Natl. Acad. Sci. U.S.A.
Neuroscience
Neuroreport
Proc. Natl. Acad. Sci. U.S.A.
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