ArticleJournal of the American Society of Nephrology : JASN2012
Triazolothienopyrimidine inhibitors of urea transporter UT-B reduce urine concentration.
Article in Journal of the American Society of Nephrology : JASN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 54 citations in OpenAlex.
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- Urea functions as a risk signal driving astrocyte-mediated neuroinflammation following stroke.Journal of neuroinflammation · 2025Article
- Ammonia transport mediated by urea transporter A isoforms.Biology open · 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
- Heavy metal bioremediation using microbially induced carbonate precipitation: Key factors and enhancement strategies.Frontiers in microbiology · 2023Review
- 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
- Inhibition of Urea Transporter (UT)-B Modulates LPS-Induced Inflammatory Responses in BV2 Microglia and N2a Neuroblastoma Cells.Neurochemical research · 2021Article
- Discovery of novel diarylamides as orally active diuretics targeting urea transporters.Acta pharmaceutica Sinica. B · 2021Article
- Urea-aromatic interactions in biology.Biophysical reviews · 2020Review
- 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
- Emerging Targets of Diuretic Therapy.Clinical pharmacology and therapeutics · 2017Review
- Imaging Renal Urea Handling in Rats at Millimeter Resolution using Hyperpolarized Magnetic Resonance Relaxometry.Tomography (Ann Arbor, Mich.) · 2016Article
- Small-molecule CFTR activators increase tear secretion and prevent experimental dry eye disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- 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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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Urea transport (UT) proteins facilitate the concentration of urine by the kidney, suggesting that inhibition of these proteins could have therapeutic use as a diuretic strategy. We screened 100,000 compounds for UT-B inhibition using an optical assay based on the hypotonic lysis of acetamide-loaded mouse erythrocytes. We identified a class of triazolothienopyrimidine UT-B inhibitors; the most potent compound, UTB(inh)-14, fully and reversibly inhibited urea transport with IC(50) values of 10 nM and 25 nM for human and mouse UT-B, respectively. UTB(inh)-14 competed with urea binding at an intracellular site on the UT-B protein. UTB(inh)-14 exhibited low toxicity and high selectivity for UT-B over UT-A isoforms. After intraperitoneal administration of UTB(inh)-14 in mice to achieve predicted therapeutic concentrations in the kidney, urine osmolality after administration of 1-deamino-8-D-arginine-vasopressin was approximately 700 mosm/kg H(2)O lower in UTB(inh)-14-treated mice than vehicle-treated mice. UTB(inh)-14 also increased urine output and reduced urine osmolality in mice given free access to water. UTB(inh)-14 did not reduce urine osmolality in UT-B knockout mice. In summary, these data provide proof of concept for the potential utility of UT inhibitors to reduce urinary concentration in high-vasopressin, fluid-retaining conditions. The diuretic mechanism of UT inhibitors may complement the action of conventional diuretics, which target sodium transport.
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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.