Abstract
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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 30-42 |
| Number of pages | 13 |
| Journal | Trends in Pharmacological Sciences |
| Volume | 43 |
| Issue number | 1 |
| Early online date | 1 Dec 2021 |
| DOIs | |
| Publication status | Published - Jan 2022 |
Bibliographical note
© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY licenseFunding: 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.).
Keywords
- aquaporins
- edema
- fluid transport
- ion channels
- osmosis
- subcellular localization
- trafficking