| Developing potent human uric acid transporter 1 (hURAT1) inhibitors. | |
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MedLine Citation:
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PMID: 21449597 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The kidneys are a vital organ in the human body. They serve several purposes including homeostatic functions such as regulating extracellular fluid volume and maintaining acid-base and electrolyte balance and are essential regarding the excretion of metabolic waste. Furthermore, the kidneys play an important role in uric acid secretion/reabsorption. Abnormalities associated with kidney transporters have been associated with various diseases, such as gout. The current study utilized Xenopus oocytes expressing human uric acid transporter 1 (hURAT1; SLC22A12) as an in vitro method to investigate novel compounds and their ability to inhibit (14)C-uric acid uptake via hURAT1. We have prepared and tested a series of 2-ethyl-benzofuran compounds and probed the hURAT1 in vitro inhibitor structure-activity relationship. As compared to dimethoxy analogues, monophenols formed on the C ring showed the best in vitro inhibitory potential. Compounds with submicromolar (i.e., IC(50) < 1000 nM) inhibitors were prepared by brominating the corresponding phenols to produce compounds with potent uricosuric activity. |
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Authors:
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Michael F Wempe; Promsuk Jutabha; Bettina Quade; Timothy J Iwen; Morin M Frick; Ian R Ross; Peter J Rice; Naohiko Anzai; Hitoshi Endou |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-03-30 |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 54 ISSN: 1520-4804 ISO Abbreviation: J. Med. Chem. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-21 Completed Date: 2011-07-04 Revised Date: 2013-03-05 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
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Languages: eng Pagination: 2701-13 Citation Subset: IM |
Affiliation:
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School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States. Michael.Wempe@ucdenver.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Drug Design Humans Kidney / metabolism Magnetic Resonance Spectroscopy Organic Anion Transporters / antagonists & inhibitors* Organic Cation Transport Proteins / antagonists & inhibitors* Xenopus |
| Grant Support | |
ID/Acronym/Agency:
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5UL1RR025780/RR/NCRR NIH HHS; UL1 RR025780/RR/NCRR NIH HHS; UL1 RR025780-04/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Organic Anion Transporters; 0/Organic Cation Transport Proteins; 0/SLC22A12 protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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