Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID	DTD0128 Transporter Info
Gene Name	SLC19A3
Transporter Name	Thiamine transporter 2
Gene ID	80704
UniProt ID	Q9BZV2

Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)
Chemical Compound
DT Modulation1	NOG protein co-treated with Panobinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC19A3 mRNA		[5]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	NOG protein co-treated with Valproic Acid co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC19A3 mRNA		[5]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Valproic Acid affects the expression of SLC19A3 mRNA		[35]
Regulation Mechanism			Transcription Factor Info
DT Modulation1	Benzo(a)pyrene results in increased methylation of SLC19A3 5' UTR		[24]
Regulation Mechanism			Transcription Factor Info
1-Methyl-4-phenylpyridinium	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	SLC19A3 protein results in increased uptake of 1-Methyl-4-phenylpyridinium		[21]
Regulation Mechanism			Transcription Factor Info
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	NOG protein co-treated with Panobinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC19A3 mRNA		[5]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	NOG protein co-treated with Valproic Acid co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC19A3 mRNA		[5]
Regulation Mechanism			Transcription Factor Info
abrine	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	abrine results in decreased expression of SLC19A3 mRNA		[22]
Regulation Mechanism			Transcription Factor Info
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate results in decreased expression of SLC19A3 mRNA		[18]
Regulation Mechanism			Transcription Factor Info
Amprolium	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Amprolium inhibits the reaction SLC19A3 protein results in increased uptake of Metformin		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Amprolium inhibits the reaction SLC19A3 protein results in increased uptake of Thiamine		[21]
Regulation Mechanism			Transcription Factor Info
beta-Naphthoflavone	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	beta-Naphthoflavone results in decreased expression of SLC19A3 mRNA		[19]
Regulation Mechanism			Transcription Factor Info
bisphenol A	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	bisphenol A co-treated with Fulvestrant results in decreased methylation of SLC19A3 gene		[25]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	bisphenol A results in increased expression of SLC19A3 mRNA		[17]
Regulation Mechanism			Transcription Factor Info
bisphenol S	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	bisphenol S results in increased expression of SLC19A3 mRNA		[17]
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 SLC19A3 mRNA		[26]
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 SLC19A3 gene		[27]
Regulation Mechanism			Transcription Factor Info
Chloroquine	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Chloroquine inhibits the reaction SLC19A3 protein results in increased uptake of Metformin		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Chloroquine inhibits the reaction SLC19A3 protein results in increased uptake of Thiamine		[21]
Regulation Mechanism			Transcription Factor Info
Deferoxamine	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Deferoxamine results in decreased expression of SLC19A3 mRNA		[28]
Regulation Mechanism			Transcription Factor Info
dorsomorphin	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	NOG protein co-treated with Panobinostat co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC19A3 mRNA		[5]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	NOG protein co-treated with Valproic Acid co-treated with dorsomorphin co-treated with 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide results in increased expression of SLC19A3 mRNA		[5]
Regulation Mechanism			Transcription Factor Info
entinostat	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	entinostat results in increased expression of SLC19A3 mRNA		[5]
Regulation Mechanism			Transcription Factor Info
Estradiol	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Estradiol co-treated with TGFB1 protein results in decreased expression of SLC19A3 mRNA		[29]
Regulation Mechanism			Transcription Factor Info
Famotidine	3 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Famotidine inhibits the reaction SLC19A3 protein results in increased uptake of Metformin		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Famotidine inhibits the reaction SLC19A3 protein results in increased uptake of Thiamine		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation3	SLC19A3 protein results in increased uptake of Famotidine		[21]
Regulation Mechanism			Transcription Factor Info
FR900359	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	FR900359 results in decreased phosphorylation of SLC19A3 protein		[30]
Regulation Mechanism			Transcription Factor Info
Fulvestrant	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	bisphenol A co-treated with Fulvestrant results in decreased methylation of SLC19A3 gene		[25]
Regulation Mechanism			Transcription Factor Info
Oxygen	3 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	HIF1A protein affects the reaction Oxygen deficiency results in decreased expression of SLC19A3 protein		[28]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Oxygen deficiency results in decreased expression of SLC19A3 mRNA		[28]
Regulation Mechanism			Transcription Factor Info
DT Modulation3	Oxygen deficiency results in decreased expression of SLC19A3 protein		[28]
Regulation Mechanism			Transcription Factor Info
perfluorooctane sulfonic acid	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	perfluorooctane sulfonic acid results in decreased expression of SLC19A3 mRNA		[18]
Regulation Mechanism			Transcription Factor Info
perfluorooctanoic acid	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	perfluorooctanoic acid results in decreased expression of SLC19A3 mRNA		[18]
Regulation Mechanism			Transcription Factor Info
Phenformin	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Phenformin inhibits the reaction SLC19A3 protein results in increased uptake of Metformin		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Phenformin inhibits the reaction SLC19A3 protein results in increased uptake of Thiamine		[21]
Regulation Mechanism			Transcription Factor Info
pirinixic acid	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	pirinixic acid binds to and results in increased activity of PPARA protein which results in increased expression of SLC19A3 mRNA		[32]
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 affects the methylation of SLC19A3 gene		[33]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	sodium arsenite results in increased expression of SLC19A3 mRNA		[15]
Regulation Mechanism			Transcription Factor Info
Thiamine	9 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Amprolium inhibits the reaction SLC19A3 protein results in increased uptake of Thiamine		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Chloroquine inhibits the reaction SLC19A3 protein results in increased uptake of Thiamine		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation3	Famotidine inhibits the reaction SLC19A3 protein results in increased uptake of Thiamine		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation4	Metformin inhibits the reaction SLC19A3 protein results in increased uptake of Thiamine		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation5	Phenformin inhibits the reaction SLC19A3 protein results in increased uptake of Thiamine		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation6	SLC19A3 protein results in increased uptake of Thiamine		[34]
Regulation Mechanism			Transcription Factor Info
DT Modulation7	Thiamine deficiency results in increased expression of SLC19A3 mRNA		[34]
Regulation Mechanism			Transcription Factor Info
DT Modulation8	Thiamine deficiency results in increased expression of SLC19A3 protein		[34]
Regulation Mechanism			Transcription Factor Info
DT Modulation9	Verapamil inhibits the reaction SLC19A3 protein results in increased uptake of Thiamine		[21]
Regulation Mechanism			Transcription Factor Info
trichostatin A	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	trichostatin A results in increased expression of SLC19A3 mRNA		[16]
Regulation Mechanism			Transcription Factor Info
Verapamil	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Verapamil inhibits the reaction SLC19A3 protein results in increased uptake of Metformin		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Verapamil inhibits the reaction SLC19A3 protein results in increased uptake of Thiamine		[21]
Regulation Mechanism			Transcription Factor Info
Vitamin K 3	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Vitamin K 3 affects the expression of SLC19A3 mRNA		[2]
Regulation Mechanism			Transcription Factor Info
Mycotoxins
aflatoxin B2	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	aflatoxin B2 results in decreased methylation of SLC19A3 intron		[23]
Regulation Mechanism			Transcription Factor Info
Approved Drug
Phenobarbital	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Phenobarbital affects the expression of SLC19A3		[1]
Hydrogen Peroxide	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Hydrogen Peroxide affects the expression of SLC19A3		[2]
Menadione	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Menadione affects the expression of SLC19A3		[2]
Zidovudine	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Zidovudine inhibits the expression of SLC19A3		[3]
Panobinostat	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Panobinostat increases the expression of SLC19A3		[4]
Vorinostat	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Vorinostat increases the expression of SLC19A3		[5]
Cisplatin	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Cisplatin inhibits the expression of SLC19A3		[6]
Urethane	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Urethane inhibits the expression of SLC19A3		[7]
Acetaminophen	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Acetaminophen inhibits the expression of SLC19A3		[8]
Cyclosporine	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Cyclosporine inhibits the expression of SLC19A3		[9]
Valproic Acid	3 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Valproic Acid increases the expression of SLC19A3		[10]
Metformin	8 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Amprolium inhibits the reaction SLC19A3 protein results in increased uptake of Metformin		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation2	Chloroquine inhibits the reaction SLC19A3 protein results in increased uptake of Metformin		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation3	Famotidine inhibits the reaction SLC19A3 protein results in increased uptake of Metformin		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation4	Metformin inhibits the reaction SLC19A3 protein results in increased uptake of Metformin		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation5	Metformin inhibits the reaction SLC19A3 protein results in increased uptake of Thiamine		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation6	Phenformin inhibits the reaction SLC19A3 protein results in increased uptake of Metformin		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation7	SLC19A3 protein results in increased uptake of Metformin		[21]
Regulation Mechanism			Transcription Factor Info
DT Modulation8	Verapamil inhibits the reaction SLC19A3 protein results in increased uptake of Metformin		[21]
Regulation Mechanism			Transcription Factor Info
Drug in Phase 2 Trial
Ethanol	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Ethanol inhibits the expression of SLC19A3		[11]
Regulation Mechanism	via the inhibition of Transcription factor Sp1 (SP1)		Transcription Factor Info
Cell System	Mouse pancreatic acinar neoplasm cells (266-6)
MS-275	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	MS-275 increases the expression of SLC19A3		[5]
Bisphenol A	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Bisphenol A increases the expression of SLC19A3		[17]
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 increases the expression of SLC19A3		[14]
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 SLC19A3		[15]
Trichostatin A	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Trichostatin A increases the expression of SLC19A3		[16]
Investigative Drug
Beta-naphthoflavone	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Beta-naphthoflavone inhibits the expression of SLC19A3		[19]
Vitamin B1	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	[3H]Thiamine modulates the activity of SLC19A3		[20]
Acute Toxic Substance
Cadmium	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Cadmium inhibits the expression of SLC19A3		[13]
Carcinogen
Benzo(a)pyrene	2 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Benzo(a)pyrene inhibits the expression of SLC19A3		[12]
Nickel	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Nickel results in decreased expression of SLC19A3 mRNA		[31]
Regulation Mechanism			Transcription Factor Info
Health and Environmental Toxicant
Perfluorooctane sulfonic acid	1 DT Activity Modulations Related to This Exogenous Factor	Click to Show/Hide the Full List
DT Modulation1	Perfluorooctane sulfonic acid inhibits the expression of SLC19A3		[18]

References
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2	Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203.
3	Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23.
4	A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
5	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
6	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
7	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
8	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
9	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.
10	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.
11	Mechanisms involved in the inhibitory effect of chronic alcohol exposure on pancreatic acinar thiamin uptake. Am J Physiol Gastrointest Liver Physiol. 2014 Apr 1;306(7):G631-9.
12	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.
13	Microarray analysis of gene expression patterns in human proximal tubule cells over a short and long time course of cadmium exposure. J Toxicol Environ Health A. 2011;74(1):24-42.
14	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.
15	Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer. Metallomics. 2012 Aug;4(8):784-93.
16	From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
17	Bisphenol A and Bisphenol S Induce Distinct Transcriptional Profiles in Differentiating Human Primary Preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
18	An assessment of serum-dependent impacts on intracellular accumulation and genomic response of per- and polyfluoroalkyl substances in a placental trophoblast model. Environ Toxicol. 2020 Dec;35(12):1395-1405.
19	Aryl hydrocarbon receptor (AhR) agonist beta-naphthoflavone regulated gene networks in human primary trophoblasts. Reprod Toxicol. 2020 Sep;96:370-379.
20	SLC19A3 encodes a second thiamine transporter ThTr2. Biochim Biophys Acta. 2001 Nov 29;1537(3):175-8.
21	Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3). Mol Pharm. 2015 Dec 7;12(12):4301-10.
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Detail Information of Exogenous Modulation

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