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.