Rapid Identification of Novel Inhibitors of the Human Aquaporin-1 Water Channel
Rajkumar V. Patil, Shouxi Xu, Alfred N. van Hoek, Andrew Rusinko, Zixia Feng, Jesse May, Mark Hellberg, Najam A. Sharif, Martin B. Wax, Macarena Irigoyen, Grant Carr, Tom Brittain, Peter Brown, Damon Colbert, Sindhu Kumari, Kulandaiappan Varadaraj and Alok K. Mitra
Article first published online: 17 JAN 2016 | DOI: 10.1111/cbdd.12713
Aquaporin (AQP) channels play critical roles in several normal physiological and pathological states involving rapid water transport and are therefore drug targets. A high-throughput cell-based screening on >6000 small molecular weight compounds identified several AQP1 blockers. Compared to canonical mercurial compounds, water transport assay in vesicles (Figure) identified two groups of most active novel AQP1 inhibitors, for example, a sulfonamide (compound 2), which constitute attractive leads for developing small-molecule functional modulators for human AQP1.