Therapeutic inhibitors of Urea Transporter A (UT-A) as highly effective diuretics with reduced risk of cardiac and neurological side effects for treatment of cardiovascular and renal disorders
Diuretics are a first line of therapy for about 20 million people worldwide suffering from cardiovascular and renal disorders. Most existing diuretic drugs work by suppressing electrolyte transport mechanisms in the kidney, which can produce neurological and cardiac side effects. There is an unmet clinical need for safer and more effective diuretics. The new compounds target urea transport mechanisms.
The current invention provides the additional advantages:
Scientists at the University of California San Francisco performed high-throughput screening of >150,000 compounds to discover potent and selective small-molecule inhibitors of UT-A, which can be used as safe and effective diuretic agents. Binding of the new molecules to UT-A disrupts the countercurrent multiple mechanism in kidney, inhibiting urinary concentration. The efficacy and potency of these compounds has been validated in rats.
In vitro and in vivo data
|United States Of America||Published Application||20200016147||01/16/2020||2014-175|
|United States Of America||Published Application||20170239235||08/24/2017||2014-175|
Diuretics / Diuretic therapy, Urea Transporter A / UT-A, Hyperuricemia, Hyponatremia