Recent breakthroughs and future directions in drugging aquaporins


Aquaporins are attractive targets for therapeutic intervention in the diverse conditions associated with water and solute dyshomeostasis that affect millions of patients worldwide every year. Aquaporin drug discovery has made little progress, possibly due to a range of assumptions including the intrinsic non-druggability of the aquaporin pore, compounded by issues with the reproducibility of current assays. We challenge the persistent idea that aquaporins are not druggable; the field is still in its infancy and much progress is yet to be made. Viable routes to inhibition of aquaporin function have recently been identified, including targeting their regulation as well as their pores. Identifying new aquaporin-targeted drugs for conditions associated with disrupted water and solute homeostasis will meet an urgent, unmet clinical need as no pharmacological interventions are currently available. Inhibition of hydrogen peroxide permeation through AQP1 provides a new approach to treating hypertrophic cardiomyopathies. Inhibition of AQP4 localization with the licensed drug trifluoperazine provides compelling evidence for a new approach to treating CNS edema.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
College of Health & Life Sciences
Additional Information: © 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license Funding: The authors acknowledge grants from the Biotechnology and Biological Sciences Research Council (to R.M.B. and P.K. through BB/P025927/1); Aston University (to P.K. through a 50th Anniversary Prize Fellowship); and the Australian Research Council Grant ARC DP190101745 (to A.J.Y.).
Uncontrolled Keywords: aquaporins,edema,fluid transport,ion channels,osmosis,subcellular localization,trafficking,Toxicology,Pharmacology
Publication ISSN: 1873-3735
Full Text Link:
Related URLs: https://linking ... 16561472100198X (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Review article
Published Date: 2022-01
Published Online Date: 2021-12-01
Accepted Date: 2021-10-22
Authors: Salman, Mootaz M.
Kitchen, Philip
Yool, Andrea J.
Bill, Roslyn M. (ORCID Profile 0000-0003-1331-0852)

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