SALT-SPARING UREA TRANSPORT INHIBITOR DIURETICS FOR TREATMENT OF CARDIOVASCULAR AND RENAL DISORDERS

Invention Novelty

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

Value Proposition

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:

• First-in-class small-molecule inhibitors of UT-A
• Produce strong diuresis via electrolyte- independent mechanism
• Effective at very low concentrations
• Increase safety and efficacy of diuretic therapy

Technology Description

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.

Application

• Treatment of edema associated with congestive heart failure, nephrotic syndrome, cirrhosis, and SIADH

Looking for Partners

• To develop and commercialize this technology for urea transport-targeted, salt-sparing diuretics

Stage of Development

Preclinical

Related Materials

• Esteva-Font et al. (2014), FASEB J.

Data Availability

 In vitro and in vivo data

Patent Status