Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID	DTD0027 Transporter Info
Gene Name	SLC22A12
Transporter Name	Urate anion exchanger 1
Gene ID	116085
UniProt ID	Q96S37

Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)
Chemical Compound
DT Modulation1	Losartan results in decreased activity of SLC22A12 protein			[13]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Losartan results in decreased activity of SLC22A12 protein which results in decreased abundance of Uric Acid			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	Losartan results in decreased expression of SLC22A12 mRNA			[13]
Regulation Mechanism				Transcription Factor Info
DT Modulation4	SLC22A12 protein affects the susceptibility to Losartan			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Benzbromarone affects the activity of SLC22A12 protein			[7]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Benzbromarone inhibits the reaction SLC22A12 protein results in increased uptake of Oxypurinol			[6]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	Benzbromarone inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation4	Benzbromarone results in decreased activity of SLC22A12 protein			[13]
Regulation Mechanism				Transcription Factor Info
DT Modulation5	SLC22A12 protein affects the susceptibility to Benzbromarone			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Probenecid affects the activity of SLC22A12 protein			[7]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Probenecid inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Sulfinpyrazone inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Pyrazinamide affects the activity of SLC22A12 protein			[7]
Regulation Mechanism				Transcription Factor Info
6-hydroxybenzbromarone	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	6-hydroxybenzbromarone inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	6-hydroxybenzbromarone results in decreased activity of SLC22A12 protein			[11]
Regulation Mechanism				Transcription Factor Info
benzarone	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	benzarone inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
bisphenol A	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	bisphenol A results in decreased methylation of SLC22A12 gene			[15]
Regulation Mechanism				Transcription Factor Info
Cadmium Chloride	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cadmium Chloride results in increased expression of SLC22A12 mRNA			[16]
Regulation Mechanism				Transcription Factor Info
CGP 52608	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	CGP 52608 promotes the reaction RORA protein binds to SLC22A12 gene			[17]
Regulation Mechanism				Transcription Factor Info
Chlorine	6 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Chlorine co-treated with perfluorodecanoic acid inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Chlorine co-treated with perfluoro-n-heptanoic acid inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	Chlorine co-treated with perfluoro-n-nonanoic acid inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation4	Chlorine co-treated with perfluorooctanoic acid inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation5	Chlorine inhibits the reaction SLC22A12 protein results in increased import of perfluorooctanoic acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation6	Chlorine inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
E 3040	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	E 3040 inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
Enalapril	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Enalapril inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
estrone sulfate	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC22A12 protein results in increased uptake of estrone sulfate			[19]
Regulation Mechanism				Transcription Factor Info
honokiol	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	honokiol inhibits the reaction Uric Acid results in increased expression of SLC22A12 protein			[20]
Regulation Mechanism				Transcription Factor Info
Indomethacin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Indomethacin inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
nuciferine	3 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	nuciferine analog binds to SLC22A12 protein			[20]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	nuciferine analog inhibits the reaction Uric Acid results in increased expression of SLC22A12 protein			[20]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	nuciferine binds to SLC22A12 protein			[20]
Regulation Mechanism				Transcription Factor Info
Oxypurinol	3 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Benzbromarone inhibits the reaction SLC22A12 protein results in increased uptake of Oxypurinol			[6]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	SLC22A12 protein results in increased uptake of Oxypurinol			[6]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	Uric Acid inhibits the reaction SLC22A12 protein results in increased uptake of Oxypurinol			[6]
Regulation Mechanism				Transcription Factor Info
perfluorodecanoic acid	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Chlorine co-treated with perfluorodecanoic acid inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
perfluorohexanoic acid	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC22A12 protein affects the uptake of perfluorohexanoic acid			[19]
Regulation Mechanism				Transcription Factor Info
perfluoro-n-heptanoic acid	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Chlorine co-treated with perfluoro-n-heptanoic acid inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
perfluorooctanoic acid	3 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Chlorine co-treated with perfluorooctanoic acid inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Chlorine inhibits the reaction SLC22A12 protein results in increased import of perfluorooctanoic acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	SLC22A12 protein results in increased import of perfluorooctanoic acid			[18]
Regulation Mechanism				Transcription Factor Info
Phenylbutazone	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Phenylbutazone inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
Salicylates	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Salicylates inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
sodium arsenite	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	sodium arsenite results in increased expression of SLC22A12 mRNA			[9]
Regulation Mechanism				Transcription Factor Info
Uric Acid	22 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	6-hydroxybenzbromarone inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	benzarone inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	Benzbromarone inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation4	Chlorine co-treated with perfluorodecanoic acid inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation5	Chlorine co-treated with perfluoro-n-heptanoic acid inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation6	Chlorine co-treated with perfluoro-n-nonanoic acid inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation7	Chlorine co-treated with perfluorooctanoic acid inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation8	Chlorine inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation9	E 3040 inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation10	Enalapril inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation11	honokiol inhibits the reaction Uric Acid results in increased expression of SLC22A12 protein			[20]
Regulation Mechanism				Transcription Factor Info
DT Modulation12	Indomethacin inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation13	Losartan results in decreased activity of SLC22A12 protein which results in decreased abundance of Uric Acid			[14]
Regulation Mechanism				Transcription Factor Info
DT Modulation14	nuciferine analog inhibits the reaction Uric Acid results in increased expression of SLC22A12 protein			[20]
Regulation Mechanism				Transcription Factor Info
DT Modulation15	Phenylbutazone inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation16	Probenecid inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation17	Salicylates inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation18	SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
DT Modulation19	SLC22A12 protein results in increased uptake of Uric Acid			[7]
Regulation Mechanism				Transcription Factor Info
DT Modulation20	Sulfinpyrazone inhibits the reaction SLC22A12 protein results in increased uptake of Uric Acid			[10]
Regulation Mechanism				Transcription Factor Info
DT Modulation21	Uric Acid inhibits the reaction SLC22A12 protein results in increased uptake of Oxypurinol			[6]
Regulation Mechanism				Transcription Factor Info
DT Modulation22	Uric Acid results in increased expression of SLC22A12 protein			[20]
Regulation Mechanism				Transcription Factor Info
Valproic Acid	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Valproic Acid results in increased methylation of SLC22A12 gene			[21]
Regulation Mechanism				Transcription Factor Info
Carcinogen
Arsenic	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Arsenic affects the methylation of SLC22A12 gene			[12]
Regulation Mechanism				Transcription Factor Info
Nanoparticle
perfluoro-n-nonanoic acid	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Chlorine co-treated with perfluoro-n-nonanoic acid inhibits the reaction SLC22A12 protein results in increased import of Uric Acid			[18]
Regulation Mechanism				Transcription Factor Info
Approved Drug
Losartan	6 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Losartan inhibits the transportation of Uric acid by SLC22A12 (Ki = 0.0077 microM)			[1]
Affected Drug/Substrate	Uric acid	Modulation Type	Inhibition
Cell System	Oocytes-URAT1
DT Modulation2	Losartan inhibits the transportation of Uric acid by SLC22A12 (IC50 = 570.5 microM)			[3]
Affected Drug/Substrate	Uric acid	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-URAT1
Benzbromarone	7 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Benzbromarone inhibits the transportation of Uric acid by SLC22A12 (IC50 = 0.13 microM)			[3]
Affected Drug/Substrate	Uric acid	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-URAT1
DT Modulation2	Benzbromarone inhibits the transportation of Uric acid by SLC22A12			[2]
Affected Drug/Substrate	Uric acid	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-URAT1
Lesinurad	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Lesinurad modulates the activity of SLC22A12			[4]
DT Modulation2	Lesinurad inhibits the activity of SLC22A12			[5]
Telmisartan	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Telmisartan inhibits the transportation of Uric acid by SLC22A12 (Ki = 0.0182 microM)			[1]
Affected Drug/Substrate	Uric acid	Modulation Type	Inhibition
Cell System	Oocytes-URAT1
Probenecid	3 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Probenecid inhibits the transportation of Uric acid by SLC22A12 (IC50 = 50 microM)			[2]
Affected Drug/Substrate	Uric acid	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-URAT1
Sulfinpyrazone	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Sulfinpyrazone inhibits the transportation of Uric acid by SLC22A12 (IC50 = 100 microM)			[2]
Affected Drug/Substrate	Uric acid	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-URAT1
Fenofibric acid	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Fenofibric acid inhibits the transportation of Uric acid by SLC22A12 (IC50 = 35.68 microM)			[3]
Affected Drug/Substrate	Uric acid	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-URAT1
Pyrazinamide	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Pyrazinamide affects the activity of SLC22A12			[7]
Irbesartan	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Irbesartan inhibits the activity of SLC22A12			[8]
Drug in Phase 3 Trial
Pratosartan	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Pratosartan inhibits the transportation of Uric acid by SLC22A12 (Ki = 0.0067 microM)			[1]
Affected Drug/Substrate	Uric acid	Modulation Type	Inhibition
Cell System	Oocytes-URAT1
Drug in Phase 1 Trial
Sodium arsenite	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Sodium arsenite increases the expression of SLC22A12			[9]
Investigative Drug
Morin	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Morin inhibits the transportation of Uric acid by SLC22A12 (IC50 = 2 microM)			[2]
Affected Drug/Substrate	Uric acid	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-URAT1
DT Modulation2	Morin inhibits the transportation of Uric acid by SLC22A12 (Ki = 5.74 microM)			[2]
Affected Drug/Substrate	Uric acid	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-URAT1
Uric acid	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Uric acid inhibits the transportation of Oxypurinol by SLC22A12 (IC50 = 170 microM)			[6]
Affected Drug/Substrate	Oxypurinol	Modulation Type	Inhibition
Cell System	Oocytes-URAT1

References
1	Concentration-dependent mode of interaction of angiotensin II receptor blockers with uric acid transporter. J Pharmacol Exp Ther. 2007 Jan;320(1):211-7.
2	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. Drug Metab Dispos. 2007 Jun;35(6):981-6.
3	Effect of fenofibrate on uric acid metabolism and urate transporter 1. Intern Med. 2010;49(2):89-94.
4	Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1031).
5	Lesinurad: A Review in Hyperuricaemia of Gout. Drugs Aging. 2017 May;34(5):401-410.
6	Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone. Drug Metab Dispos. 2005 Dec;33(12):1791-5.
7	Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion. J Am Soc Nephrol. 2004 Jan;15(1):164-73.
8	Concentration-dependent inhibitory effect of irbesartan on renal uric acid transporters. J Pharmacol Sci. 2010;114(1):115-8.
9	Cellular and Molecular Effects of Prolonged Low-Level Sodium Arsenite Exposure on Human Hepatic HepaRG Cells. Toxicol Sci. 2018 Apr 1;162(2):676-687.
10	Interactions of urate transporter URAT1 in human kidney with uricosuric drugs. Nephrology (Carlton). 2011;16(2):156-62.
11	Developing potent human uric acid transporter 1 (hURAT1) inhibitors. J Med Chem. 2011 Apr 28;54(8):2701-13.
12	Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106.
13	Effect of losartan and benzbromarone on the level of human urate transporter 1 mRNA. Arzneimittelforschung. 2010;60(4):186-8.
14	Uricosuric action of losartan via the inhibition of urate transporter 1 (URAT 1) in hypertensive patients. Am J Hypertens. 2008;21(10):1157-62.
15	DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
16	High-Throughput Transcriptomics of Nontumorigenic Breast Cells Exposed to Environmentally Relevant Chemicals. Environ Health Perspect. 2024;132(4):47002.
17	Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
18	Characterization of cellular uptake of perfluorooctanoate via organic anion-transporting polypeptide 1A2, organic anion transporter 4, and urate transporter 1 for their potential roles in mediating human renal reabsorption of perfluorocarboxylates. Toxicol Sci. 2010;117(2):294-302.
19	Lack of interaction of the fluorosurfactant C6O4 with human renal transporters: In vitro/in silico analysis. Toxicology. 2022;476:153257.
20	Synthesis and bioactivity evaluation of novel nuciferine derivatives with antihyperuricemia and nephroprotective effects. Bioorg Chem. 2022;126:105916.
21	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.

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Detail Information of Exogenous Modulation

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