| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T86057 | ||||
| Target Name | Solute carrier family 22 member 12 | ||||
| Target Type | Successful |
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| Drug Potency against Target | MORIN | Drug Info | IC50 = 18000 nM | [528700] | |
| Lesinurad | Drug Info | EC50 = 5000 nM | |||
| Action against Disease Model | Lesinurad | We investigated the effect of URAT-1 inhibitor losartan (0.2 mM) on K562 cell line | Drug Info | ||
| The Effect of Target Knockout, Knockdown or Genetic Variations | Organic anion transporters (Oats) are located in the barrier epithelia of diverse organs, where they mediate the absorption and excretion of a wide range of metabolites, signaling molecules, and xenobiotics. Although their interactions with a broad group of substrates have been extensively studied and described, the primary physiological role of Oats remains elusive. The presence of overlapping substrate specificities among the different Oat isoforms, together with recent metabolomic data from the Oat1, Oat3, and renal-specific transporter (RST/URAT1) knockout mice, suggests a possible role in remote signaling wherein substrates excreted through one Oat isoform in one organ are taken up by another Oat isoform located in a different organ, thereby mediating communication between different organ systems, or even between different organisms. Here we further develop this "remote sensing and signaling hypothesis" and suggest how the regulation of SLC22 subfamily members (including those of the organic cation, organic carnitine, and unknown substrate transporter subfamilies) can be better understood by considering the organism's broader need to communicate between epithelial and other tissues by simultaneous regulation of transport of metabolites, signaling molecules, drugs, and toxins. This systems biology perspective of remote signaling (sensing) could help reconcile an enormous array of tissue-specific data for various SLC22 family genes and, possibly, other multispecific transporters, such as those of the organic anion transporting polypeptide (OATP, SLC21) and multidrug resistance-associated protein (MRP) families. | ||||
| References | |||||
| Ref 528700 | Drug Metab Dispos. 2007 Jun;35(6):981-6. Epub 2007 Feb 26.Morin (3,5,7,2',4'-pentahydroxyflavone) exhibits potent inhibitory actions on urate transport by the human urate anion transporter (hURAT1) expressed in human embryonic kidney cells. | ||||
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