ArticleAmerican journal of physiology. Renal physiology2014
Thienoquinolins exert diuresis by strongly inhibiting UT-A urea transporters.
Article in American journal of physiology. Renal physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Epithelial plasma membrane transporters as drug targets.Physiological reviews · 2026Review
- Small-Molecule Inhibitors and Drug Discovery of Urea Transporters.Sub-cellular biochemistry · 2025Review
- Urea Transporter Inhibitor 25a Reduces Ascites in Cirrhotic Rats.Biomedicines · 2023Article
- Discovery of novel diarylamides as orally active diuretics targeting urea transporters.Acta pharmaceutica Sinica. B · 2021Article
- The urea transporter UT-A1 plays a predominant role in a urea-dependent urine-concentrating mechanism.The Journal of biological chemistry · 2020Article
- A mouse model of subacute liver failure with ascites induced by step-wise increased doses of (-)-epigallocatechin-3-gallate.Scientific reports · 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
- Urea transport and clinical potential of urearetics.Current opinion in nephrology and hypertension · 2016Review
- Phenylphthalazines as small-molecule inhibitors of urea transporter UT-B and their binding model.Acta pharmacologica Sinica · 2016Article
- Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
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Abstract
Urea transporters (UT) play an important role in the urine concentration mechanism by mediating intrarenal urea recycling, suggesting that UT inhibitors could have therapeutic use as a novel class of diuretic. Recently, we found a thienoquinolin UT inhibitor, PU-14, that exhibited diuretic activity. The purpose of this study was to identify more potent UT inhibitors that strongly inhibit UT-A isoforms in the inner medullary collecting duct (IMCD). Efficient thienoquinolin UT inhibitors were identified by structure-activity relationship analysis. Urea transport inhibition activity was assayed in perfused rat terminal IMCDs. Diuretic activity of the compound was determined in rats and mice using metabolic cages. The results show that the compound PU-48 exhibited potent UT-A inhibition activity. The inhibition was 69.5% with an IC50 of 0.32 μM. PU-48 significantly inhibited urea transport in perfused rat terminal IMCDs. PU-48 caused significant diuresis in UT-B null mice, which indicates that UT-A is the target of PU-48. The diuresis caused by PU-48 did not change blood Na(+), K(+), or Cl(-) levels or nonurea solute excretion in rats and mice. No toxicity was detected in cells or animals treated with PU-48. The results indicate that thienoquinolin UT inhibitors induce a diuresis by inhibiting UT-A in the IMCD. This suggests that they may have the potential to be developed as a novel class of diuretics with fewer side effects than classical diuretics.
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