Urea Transporters Identified as Novel Diuretic Drug Targets

Author(s): Min Li, Shun Zhang, Baoxue Yang*.

Journal Name: Current Drug Targets

Volume 21 , Issue 3 , 2020

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Graphical Abstract:


Abstract:

Background: Urea Transporters are a family of membrane channel proteins that facilitate the passive transport of urea across the plasma membrane. UTs are divided into two subgroups, UT-A and UT-B. UT-As are primarily located in renal tubule epithelia and UT-Bs are highly expressed in renal descending vasa recta and extrarenal multiple tissues. Various urea transporter knockout mice exhibit low urine concentrating ability, which suggests that UTs are novel diuretic targets. With highthroughput screening of small molecule drug-like compound libraries, various potent UT inhibitors with IC50 at nanomolar level were identified. Furthermore, selective UT inhibitors exhibit diuretic activity without disturbing electrolyte and metabolism balance, which confirms the potential of UTs as diuretic targets and UT inhibitors as novel diuretics that do not cause electrolyte imbalance.

Objective: This review article summarizes the identification and validation of urea transporter as a potential diuretic target and the discovery of small molecule UT inhibitors as a novel type of diuretics.

Conclusion: UTs are a potential diuretic target. UT inhibitors play significant diuresis and can be developed to diuretics without disturbing electrolyte balance.

Keywords: Urea transporter, diuretic target, inhibitor, drug discovery, molecular dynamics, electrolyte balance.

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VOLUME: 21
ISSUE: 3
Year: 2020
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DOI: 10.2174/1389450120666191129101915
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