Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID	DTD0152 Transporter Info
Gene Name	SLC22A9
Transporter Name	Organic anion transporter 7
Gene ID	114571
UniProt ID	Q8IVM8

Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)
Chemical Compound
DT Modulation1	Diclofenac results in decreased activity of SLC22A9 protein		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Indomethacin results in decreased activity of SLC22A9 protein		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	SLC22A9 protein results in increased uptake of Indomethacin		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Ketoprofen results in decreased activity of SLC22A9 protein		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	SLC22A9 protein results in increased uptake of Ketoprofen		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Mefenamic Acid results in decreased activity of SLC22A9 protein		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Naproxen results in decreased activity of SLC22A9 protein		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Piroxicam results in decreased activity of SLC22A9 protein		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Sulindac results in decreased activity of SLC22A9 protein		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Salicylic Acid results in decreased activity of SLC22A9 protein		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	SLC22A9 protein results in increased uptake of Salicylic Acid		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Progesterone affects the localization of SLC22A9 protein		[2]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Progesterone results in decreased activity of SLC22A9 protein		[2]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Probenecid inhibits the reaction SLC22A9 protein results in increased import of estrone sulfate		[9]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Probenecid inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
DT Modulation3	Probenecid results in decreased activity of SLC22A9 protein		[9]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Valproic Acid results in decreased methylation of SLC22A9 gene		[11]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Phenacetin results in decreased activity of SLC22A9 protein		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Benzo(a)pyrene affects the methylation of SLC22A9 promoter		[18]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Benzo(a)pyrene results in increased methylation of SLC22A9 3' UTR		[18]
Regulation Mechanism			Transcription Factor Info
DT Modulation3	Benzo(a)pyrene results in increased methylation of SLC22A9 5' UTR		[18]
Regulation Mechanism			Transcription Factor Info
4-O-methyl-12-O-tetradecanoylphorbol 13-acetate	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	4-O-methyl-12-O-tetradecanoylphorbol 13-acetate results in decreased activity of SLC22A9 protein		[2]
Regulation Mechanism			Transcription Factor Info
candesartan	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	candesartan inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
candesartan cilexetil	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	candesartan cilexetil inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
Dehydroepiandrosterone Sulfate	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Dehydroepiandrosterone Sulfate inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
estrone sulfate	12 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	candesartan cilexetil inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	candesartan inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
DT Modulation3	Dehydroepiandrosterone Sulfate inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
DT Modulation4	losartan carboxylic acid inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
DT Modulation5	Losartan inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
DT Modulation6	pranlukast inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
DT Modulation7	Probenecid inhibits the reaction SLC22A9 protein results in increased import of estrone sulfate		[9]
Regulation Mechanism			Transcription Factor Info
DT Modulation8	Probenecid inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
DT Modulation9	SLC22A9 protein results in increased import of estrone sulfate		[9]
Regulation Mechanism			Transcription Factor Info
DT Modulation10	SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
DT Modulation11	Tobacco Smoke Pollution inhibits the reaction SLC22A9 protein results in increased import of estrone sulfate		[9]
Regulation Mechanism			Transcription Factor Info
DT Modulation12	Valsartan inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
heliotrine	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	heliotrine results in decreased expression of SLC22A9 mRNA		[13]
Regulation Mechanism			Transcription Factor Info
Losartan	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Losartan inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
losartan carboxylic acid	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	losartan carboxylic acid inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
methyleugenol	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	methyleugenol results in decreased expression of SLC22A9 mRNA		[15]
Regulation Mechanism			Transcription Factor Info
Okadaic Acid	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Okadaic Acid results in decreased expression of SLC22A9 mRNA		[20]
Regulation Mechanism			Transcription Factor Info
OTX015	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	OTX015 results in decreased expression of SLC22A9 mRNA		[21]
Regulation Mechanism			Transcription Factor Info
Phorbol 12,13-Dibutyrate	4 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Phorbol 12,13-Dibutyrate affects the localization of SLC22A9 protein		[2]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Phorbol 12,13-Dibutyrate results in decreased activity of SLC22A9 protein		[2]
Regulation Mechanism			Transcription Factor Info
DT Modulation3	Staurosporine inhibits the reaction Phorbol 12,13-Dibutyrate affects the localization of SLC22A9 protein		[2]
Regulation Mechanism			Transcription Factor Info
DT Modulation4	Staurosporine inhibits the reaction Phorbol 12,13-Dibutyrate results in decreased activity of SLC22A9 protein		[2]
Regulation Mechanism			Transcription Factor Info
pranlukast	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	pranlukast inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
senecionine	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	senecionine results in decreased expression of SLC22A9 mRNA		[13]
Regulation Mechanism			Transcription Factor Info
senkirkine	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	senkirkine results in decreased expression of SLC22A9 mRNA		[13]
Regulation Mechanism			Transcription Factor Info
sodium arsenite	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	sodium arsenite results in decreased expression of SLC22A9 mRNA		[14]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	sodium arsenite results in increased expression of SLC22A9 mRNA		[22]
Regulation Mechanism			Transcription Factor Info
Staurosporine	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Staurosporine inhibits the reaction Phorbol 12,13-Dibutyrate affects the localization of SLC22A9 protein		[2]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Staurosporine inhibits the reaction Phorbol 12,13-Dibutyrate results in decreased activity of SLC22A9 protein		[2]
Regulation Mechanism			Transcription Factor Info
Tetracycline	3 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	SLC22A9 protein results in increased export of Tetracycline		[23]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	SLC22A9 protein results in increased uptake of Tetracycline		[23]
Regulation Mechanism			Transcription Factor Info
DT Modulation3	Tetracycline inhibits the reaction SLC22A9 protein results in increased uptake of Anions		[23]
Regulation Mechanism			Transcription Factor Info
Valsartan	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Valsartan inhibits the reaction SLC22A9 protein results in increased uptake of estrone sulfate		[19]
Regulation Mechanism			Transcription Factor Info
Approved Drug
Acetaminophen	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Acetaminophen inhibits the activity of SLC22A9		[1]
DT Modulation2	Acetaminophen results in decreased activity of SLC22A9 protein		[1]
Regulation Mechanism			Transcription Factor Info
Aspirin	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Aspirin inhibits the activity of SLC22A9		[1]
DT Modulation2	Aspirin results in decreased activity of SLC22A9 protein		[1]
Regulation Mechanism			Transcription Factor Info
Diclofenac	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Diclofenac inhibits the activity of SLC22A9		[1]
Ibuprofen	3 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Ibuprofen inhibits the activity of SLC22A9		[1]
DT Modulation2	Ibuprofen results in decreased activity of SLC22A9 protein		[1]
Regulation Mechanism			Transcription Factor Info
DT Modulation3	SLC22A9 protein results in increased uptake of Ibuprofen		[1]
Regulation Mechanism			Transcription Factor Info
Indomethacin	3 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Indomethacin inhibits the activity of SLC22A9		[1]
Ketoprofen	3 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Ketoprofen inhibits the activity of SLC22A9		[1]
Mefenamic Acid	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Mefenamic Acid inhibits the activity of SLC22A9		[1]
Naproxen	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Naproxen inhibits the activity of SLC22A9		[1]
Piroxicam	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Piroxicam inhibits the activity of SLC22A9		[1]
Sulindac	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Sulindac inhibits the activity of SLC22A9		[1]
Progesterone	3 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Progesterone inhibits the activity of SLC22A9		[2]
Phenobarbital	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Phenobarbital affects the expression of SLC22A9		[3]
Copper Sulfate	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Copper Sulfate inhibits the expression of SLC22A9		[4]
Estradiol	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Estradiol inhibits the expression of SLC22A9		[5]
Zidovudine	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Zidovudine inhibits the expression of SLC22A9		[6]
Rosiglitazone	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Rosiglitazone inhibits the expression of SLC22A9		[7]
Rifampin	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Rifampin inhibits the expression of SLC22A9		[8]
Probenecid	4 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Probenecid inhibits the activity of SLC22A9		[9]
Urethane	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Urethane inhibits the expression of SLC22A9		[10]
Valproic Acid	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Valproic Acid inhibits the expression of SLC22A9		[11]
Cyclosporine	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Cyclosporine inhibits the expression of SLC22A9		[12]
Drug in Phase 2/3 Trial
Salicylic Acid	3 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Salicylic Acid inhibits the activity of SLC22A9		[1]
Drug in Phase 1 Trial
Quercetin	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Quercetin inhibits the expression of SLC22A9		[5]
Sodium arsenite	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Sodium arsenite inhibits the expression of SLC22A9		[14]
Drug Withdrawn
Phenacetin	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Phenacetin inhibits the activity of SLC22A9		[1]
Natural Product
Heliotrine	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Heliotrine inhibits the expression of SLC22A9		[13]
Senecionine	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Senecionine inhibits the expression of SLC22A9		[13]
Tobacco Smoke Pollution	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Tobacco Smoke Pollution inhibits the activity of SLC22A9		[9]
Methyleugenol	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Methyleugenol inhibits the expression of SLC22A9		[15]
Mycotoxins
Aflatoxin B1	3 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Aflatoxin B1 inhibits the expression of SLC22A9		[16]
DT Modulation2	Aflatoxin B1 affects the expression of SLC22A9 protein		[17]
Regulation Mechanism			Transcription Factor Info
DT Modulation3	Aflatoxin B1 results in decreased methylation of SLC22A9 gene		[16]
Regulation Mechanism			Transcription Factor Info
Carcinogen
Benzo(a)pyrene	4 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Benzo(a)pyrene inhibits the expression of SLC22A9		[15]

References
1	Interactions of human organic anion transporters and human organic cation transporters with nonsteroidal anti-inflammatory drugs. J Pharmacol Exp Ther. 2002 Nov;303(2):534-9.
2	Regulation of human organic anion transporter 4 by progesterone and protein kinase C in human placental BeWo cells. Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E57-61.
3	Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75.
4	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
5	Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
6	Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23.
7	Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
8	Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
9	Inhibition of organic anion transporter (OAT) activity by cigarette smoke condensate. Toxicol In Vitro. 2017 Oct;44:27-35.
10	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
11	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.
12	Integrative "-Omics" Analysis in Primary Human Hepatocytes Unravels Persistent Mechanisms of Cyclosporine A-Induced Cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
13	Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis. Toxicol In Vitro. 2015 Oct;29(7):1669-82.
14	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.
15	Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297.
16	Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
17	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
18	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
19	Inhibitory effects of angiotensin II receptor antagonists and leukotriene receptor antagonists on the transport of human organic anion transporter 4. J Pharm Pharmacol. 2006 Nov;58(11):1499-505.
20	A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells. Arch Toxicol. 2024;98(9):2919-2935.
21	Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022;17(4):e0266966.
22	High-Throughput Transcriptomics of Nontumorigenic Breast Cells Exposed to Environmentally Relevant Chemicals. Environ Health Perspect. 2024;132(4):47002.
23	Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76.

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Detail Information of Exogenous Modulation

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