Recent breakthroughs and future directions in drugging aquaporins.

Mootaz M Salman, Philip Kitchen, Andrea J Yool, Roslyn M Bill

Journal: Trends in pharmacological sciences 2022;43(1):30-42

PMID: 34863533

Free Full Text on Elsevier Science View on PubMed

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.

Address: 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: [email protected].; School of Biosciences, College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK. Electronic address: [email protected].; University of Adelaide, School of Biomedicine, Adelaide, South Australia 5005, Australia. Electronic address: [email protected].; School of Biosciences, College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK. Electronic address: [email protected].

DOI: 10.1016/j.tips.2021.10.009