Developing potent human uric acid transporter 1 (hURAT1) inhibitors.

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Wempe MF, Jutabha P, Quade B, Iwen TJ, Frick MM, Ross IR, Rice PJ, Anzai N, Endou H

Developing potent human uric acid transporter 1 (hURAT1) inhibitors.

J Med Chem. 2011 Apr 28;54(8):2701-13. doi: 10.1021/jm1015022. Epub 2011 Mar 30.

PubMed ID

21449597 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Probenecid	Solute carrier family 22 member 12	IC 50 (nM)	86390	N/A	N/A	Details