2. Academic Validation
  3. Recent breakthroughs and future directions in drugging aquaporins

Recent breakthroughs and future directions in drugging aquaporins

  • Trends Pharmacol Sci. 2022 Jan;43(1):30-42. doi: 10.1016/j.tips.2021.10.009.
Mootaz M Salman 1,  Philip Kitchen 2,  Andrea J Yool 3,  Roslyn M Bill 4
Affiliations

Affiliations

  • 1 Department of Physiology, Anatomy and Genetics, Kavli Institute for NanoScience Discovery, University of Oxford, Oxford OX1 3PT, UK; Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK. Electronic address: mootaz.salman@dpag.ox.ac.uk.
  • 2 School of Biosciences, College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK. Electronic address: p.kitchen1@aston.ac.uk.
  • 3 University of Adelaide, School of Biomedicine, Adelaide, South Australia 5005, Australia. Electronic address: andrea.yool@adelaide.edu.au.
  • 4 School of Biosciences, College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK. Electronic address: r.m.bill@aston.ac.uk.
PMID: 34863533 DOI: 10.1016/j.tips.2021.10.009
Abstract

Aquaporins facilitate the passive transport of water, solutes, or ions across biological membranes. They are implicated in diverse pathologies including brain edema following stroke or trauma, epilepsy, Cancer cell migration and tumor angiogenesis, metabolic disorders, and inflammation. Despite this, there is no aquaporin-targeted drug in the clinic and aquaporins have been perceived to be intrinsically non-druggable targets. Here we challenge this idea, as viable routes to inhibition of Aquaporin function have recently been identified, including targeting their regulation or their roles as channels for unexpected substrates. Identifying new drug development frameworks for conditions associated with disrupted water and solute homeostasis will meet the urgent, unmet clinical need of millions of patients for whom no pharmacological interventions are available.

Keywords

aquaporins; edema; fluid transport; ion channels; osmosis; subcellular localization; trafficking.

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