title: Small-molecule inhibitors of urea transporters.
abstract: Urea transporter (UT) proteins, which include isoforms of UT-A in kidney tubule epithelia and UT-B in vasa recta endothelia and erythrocytes, facilitate urinary concentrating function. Inhibitors of urea transporter function have potential clinical applications as sodium-sparing diuretics, or 'urearetics,' in edema from different etiologies, such as congestive heart failure and cirrhosis, as well as in syndrome of inappropriate antidiuretic hormone (SIADH). High-throughput screening of drug-like small molecules has identified UT-A and UT-B inhibitors with nanomolar potency. Inhibitors have been identified with different UT-A versus UT-B selectivity profiles and putative binding sites on UT proteins. Studies in rodent models support the utility of UT inhibitors in reducing urinary concentration, though testing in clinically relevant animal models of edema has not yet been done.
authors.affiliation: Departments of Medicine and Physiology, University of California, San Francisco, CA, 94143-0521, USA, alan.verkman@ucsf.edu.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Verkman
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteva-Font
authors.forename: Onur
authors.initials: O
authors.lastname: Cil
authors.forename: Marc O
authors.initials: MO
authors.lastname: Anderson
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Tianluo
authors.initials: T
authors.lastname: Lei
authors.forename: Huiwen
authors.initials: H
authors.lastname: Ren
authors.forename: Baoxue
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D014508:Urea / Q000737:chemistry* / Q000378:metabolism; D000096982:Urea Transporters
chemical_list: D026901:Membrane Transport Proteins; D054852:Small Molecule Libraries; D014508:Urea; D000096982:Urea Transporters