ArticleChemistry & biology2013
A small molecule screen identifies selective inhibitors of urea transporter UT-A.
Article in Chemistry & biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- Design, Synthesis, and Biological Evaluation of Naphthoquinone Salts as Anticancer Agents.Molecules (Basel, Switzerland) · 2025Article
- Druggability Studies of Benzene Sulfonamide Substituted Diarylamide (E3) as a Novel Diuretic.Biomedicines · 2025Article
- Identification and Validation of Urea Transporter B Inhibitor fromMolecules (Basel, Switzerland) · 2025Article
- Small-Molecule Inhibitors and Drug Discovery of Urea Transporters.Sub-cellular biochemistry · 2025Review
- Protein Structures of Urea Transporters.Sub-cellular biochemistry · 2025Review
- Structural insights into the mechanisms of urea permeation and distinct inhibition modes of urea transporters.Nature communications · 2024Article
- A critical analysis of urea transporter B inhibitors: molecular fingerprints, pharmacophore features for the development of next-generation diuretics.Molecular diversity · 2022Article
- Preclinical Pharmacokinetic Studies of a Novel Diuretic Inhibiting Urea Transporters.Molecules (Basel, Switzerland) · 2022Article
- Aquaglyceroporin Modulators as Emergent Pharmacological Molecules for Human Diseases.Frontiers in molecular biosciences · 2022Review
- Water transport mediated by murine urea transporters: implications for urine concentration mechanisms.Biology open · 2020Article
- A mouse model of subacute liver failure with ascites induced by step-wise increased doses of (-)-epigallocatechin-3-gallate.Scientific reports · 2019Article
- Inhibitors of Mammalian Aquaporin Water Channels.International journal of molecular sciences · 2019Review
- Lack of urea transporters, UT-A1 and UT-A3, increases nitric oxide accumulation to dampen medullary sodium reabsorption through ENaC.American journal of physiology. Renal physiology · 2019Article
- Pharmacokinetics, Tissue Distribution and Excretion of a Novel Diuretic (PU-48) in Rats.Pharmaceutics · 2018Article
- Nanomolar-Potency 1,2,4-Triazoloquinoxaline Inhibitors of the Kidney Urea Transporter UT-A1.Journal of medicinal chemistry · 2018Article
- Generation and phenotypic analysis of mice lacking all urea transporters.Kidney international · 2017Article
- Salt-sparing diuretic action of a water-soluble urea analog inhibitor of urea transporters UT-A and UT-B in rats.Kidney international · 2015Article
- Structure-activity analysis of thiourea analogs as inhibitors of UT-A and UT-B urea transporters.Biochimica et biophysica acta · 2015Article
- Urea transporter proteins as targets for small-molecule diuretics.Nature reviews. Nephrology · 2015Review
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4 authors at 2 institutions in 1 country.
Funding
Abstract
Urea transporter (UT) proteins, including UT-A in kidney tubule epithelia and UT-B in vasa recta microvessels, facilitate urinary concentrating function. A screen for UT-A inhibitors was developed in MDCK cells expressing UT-A1, water channel aquaporin-1, and YFP-H148Q/V163S. An inwardly directed urea gradient produces cell shrinking followed by UT-A1-dependent swelling, which was monitored by YFP-H148Q/V163S fluorescence. Screening of ~90,000 synthetic small molecules yielded four classes of UT-A1 inhibitors with low micromolar half-maximal inhibitory concentration that fully and reversibly inhibited urea transport by a noncompetitive mechanism. Structure-activity analysis of >400 analogs revealed UT-A1-selective and UT-A1/UT-B nonselective inhibitors. Docking computations based on homology models of UT-A1 suggested inhibitor binding sites. UT-A inhibitors may be useful as diuretics ("urearetics") with a mechanism of action that may be effective in fluid-retaining conditions in which conventional salt transport-blocking diuretics have limited efficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.