Phenylphthalazines as small-molecule inhibitors of urea transporter UT-B and their binding model.

ABSTRACT:

Aim

Urea transporters (UT) are a family of transmembrane proteins that specifically transport urea. UT inhibitors exert diuretic activity without affecting electrolyte balance. The purpose of this study was to discover novel UT inhibitors and determine the inhibition mechanism.

Methods

The primary screening urea transporter B (UT-B) inhibitory activity was conducted in a collection of 10 000 diverse small molecules using mouse erythrocyte lysis assay. After discovering a hit with a core structure of 1-phenylamino-4-phenylphthalazin, the UT-B inhibitory activity of 160 analogs were examined with a stopped-flow light scattering assay and their structure-activity relationship (SAR) was analyzed. The inhibition mechanism was further investigated using in silico assays.

Result

SUBMITTER: Ran JH 

PROVIDER: S-EPMC4933761 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature