Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID	DTD0372 Transporter Info
Gene Name	SLC46A1
Transporter Name	Proton-coupled folate transporter
Gene ID	113235
UniProt ID	Q96NT5

Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)
Chemical Compound
DT Modulation1	Pemetrexed inhibits the reaction SLC46A1 protein results in increased uptake of Methotrexate			[1]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Pemetrexed results in increased activity of SLC46A1 protein			[1]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	SLC46A1 protein results in increased susceptibility to Pemetrexed			[1]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Leucovorin inhibits the reaction SLC46A1 protein results in increased transport of Folic Acid			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Leucovorin results in decreased activity of SLC46A1 protein			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Pyrimethamine results in decreased activity of SLC46A1 protein			[7]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Cisplatin co-treated with jinfukang results in increased expression of SLC46A1 mRNA			[11]
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 SLC46A1 mRNA			[29]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Valproic Acid results in decreased methylation of SLC46A1 gene			[47]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid inhibits the reaction SLC46A1 protein results in increased transport of Folic Acid			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	5-methyltetrahydrofolate inhibits the reaction SLC46A1 protein results in increased transport of Folic Acid			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	Folic Acid deficiency results in decreased expression of SLC46A1 mRNA			[37]
Regulation Mechanism				Transcription Factor Info
DT Modulation4	Folic Acid results in decreased expression of SLC46A1 mRNA			[38]
Regulation Mechanism				Transcription Factor Info
DT Modulation5	Leucovorin inhibits the reaction SLC46A1 protein results in increased transport of Folic Acid			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation6	Methotrexate inhibits the reaction SLC46A1 protein results in increased transport of Folic Acid			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation7	SLC46A1 protein results in increased transport of Folic Acid			[39]
Regulation Mechanism				Transcription Factor Info
DT Modulation8	Sulfobromophthalein inhibits the reaction SLC46A1 protein results in increased transport of Folic Acid			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Methotrexate inhibits the reaction SLC46A1 protein results in increased transport of Folic Acid			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Methotrexate results in decreased activity of SLC46A1 protein			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	Methotrexate results in decreased expression of SLC46A1 mRNA			[41]
Regulation Mechanism				Transcription Factor Info
DT Modulation4	N-((5-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-6-yl)propyl)thiophen-2-yl)carbonyl)glutamic acid inhibits the reaction SLC46A1 protein results in increased uptake of Methotrexate			[1]
Regulation Mechanism				Transcription Factor Info
DT Modulation5	Pemetrexed inhibits the reaction SLC46A1 protein results in increased uptake of Methotrexate			[1]
Regulation Mechanism				Transcription Factor Info
DT Modulation6	SLC46A1 gene SNP results in increased susceptibility to Methotrexate			[42]
Regulation Mechanism				Transcription Factor Info
DT Modulation7	SLC46A1 protein results in increased susceptibility to Methotrexate			[1]
Regulation Mechanism				Transcription Factor Info
DT Modulation8	SLC46A1 protein results in increased transport of Methotrexate			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation9	SLC46A1 protein results in increased uptake of Methotrexate			[1]
Regulation Mechanism				Transcription Factor Info
DT Modulation10	Sulfasalazine inhibits the reaction SLC46A1 protein results in increased transport of Methotrexate			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Sulfasalazine inhibits the reaction SLC46A1 protein results in increased transport of Methotrexate			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Sulfasalazine results in decreased activity of SLC46A1 protein			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	NOG protein co-treated with Phenylmercuric Acetate 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 SLC46A1 mRNA			[29]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Benzo(a)pyrene affects the methylation of SLC46A1 promoter			[33]
Regulation Mechanism				Transcription Factor Info
3-iodothyronamine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC46A1 mRNA affects the uptake of 3-iodothyronamine			[28]
Regulation Mechanism				Transcription Factor Info
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid inhibits the reaction SLC46A1 protein results in increased transport of Folic Acid			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid results in decreased activity of SLC46A1 protein			[4]
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 Phenylmercuric Acetate 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 SLC46A1 mRNA			[29]
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 SLC46A1 mRNA			[29]
Regulation Mechanism				Transcription Factor Info
5-methyltetrahydrofolate	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	5-methyltetrahydrofolate inhibits the reaction SLC46A1 protein results in increased transport of Folic Acid			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	5-methyltetrahydrofolate results in decreased activity of SLC46A1 protein			[4]
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 SLC46A1 mRNA			[30]
Regulation Mechanism				Transcription Factor Info
Adenosine Triphosphate	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC46A1 protein results in increased susceptibility to N-((5-((2-amino-4-oxo-4,7-dihydro-3H-pyrrolo(2,3-d)pyrimidin-6-yl)propyl)thiophen-2-yl)carbonyl)glutamic acid which results in decreased chemical synthesis of Adenosine Triphosphate			[1]
Regulation Mechanism				Transcription Factor Info
AM 251	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	AM 251 results in increased expression of SLC46A1 mRNA			[5]
Regulation Mechanism				Transcription Factor Info
apicidin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	apicidin results in increased expression of SLC46A1 mRNA			[31]
Regulation Mechanism				Transcription Factor Info
aristolochic acid I	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	aristolochic acid I results in increased expression of SLC46A1 mRNA			[32]
Regulation Mechanism				Transcription Factor Info
Cadmium Chloride	3 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cadmium Chloride results in decreased expression of SLC46A1 mRNA			[35]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Cadmium Chloride results in increased abundance of Cadmium which results in decreased expression of SLC46A1 mRNA			[34]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	Cadmium Chloride results in increased expression of SLC46A1 mRNA			[21]
Regulation Mechanism				Transcription Factor Info
Cholecalciferol	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cholecalciferol results in increased expression of SLC46A1 mRNA			[9]
Regulation Mechanism				Transcription Factor Info
Decitabine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Decitabine affects the methylation of SLC46A1 promoter which affects the expression of SLC46A1 mRNA			[36]
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 Phenylmercuric Acetate 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 SLC46A1 mRNA			[29]
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 SLC46A1 mRNA			[29]
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 affects the phosphorylation of SLC46A1 protein			[40]
Regulation Mechanism				Transcription Factor Info
Heme	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC46A1 protein promotes the reaction Heme results in increased expression of HMOX1 mRNA			[21]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	SLC46A1 protein results in increased uptake of Heme			[21]
Regulation Mechanism				Transcription Factor Info
lometrexol	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC46A1 protein results in increased susceptibility to lometrexol			[1]
Regulation Mechanism				Transcription Factor Info
Methyl Methanesulfonate	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Methyl Methanesulfonate results in increased expression of SLC46A1 mRNA			[23]
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 SLC46A1 mRNA			[43]
Regulation Mechanism				Transcription Factor Info
potassium chromate(VI)	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	potassium chromate(VI) results in increased expression of SLC46A1 mRNA			[44]
Regulation Mechanism				Transcription Factor Info
raltitrexed	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC46A1 protein results in increased susceptibility to raltitrexed			[1]
Regulation Mechanism				Transcription Factor Info
S-(1,2-dichlorovinyl)cysteine	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	S-(1,2-dichlorovinyl)cysteine affects the susceptibility to Lipopolysaccharides which results in increased expression of SLC46A1 mRNA			[45]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	S-(1,2-dichlorovinyl)cysteine co-treated with Lipopolysaccharides results in decreased expression of SLC46A1 mRNA			[45]
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 SLC46A1 mRNA			[25]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	sodium arsenite results in increased expression of SLC46A1 mRNA			[44]
Regulation Mechanism				Transcription Factor Info
Sulfobromophthalein	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Sulfobromophthalein inhibits the reaction SLC46A1 protein results in increased transport of Folic Acid			[4]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Sulfobromophthalein results in decreased activity of SLC46A1 protein			[4]
Regulation Mechanism				Transcription Factor Info
tert-Butylhydroperoxide	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	tert-Butylhydroperoxide results in decreased expression of SLC46A1 mRNA			[46]
Regulation Mechanism				Transcription Factor Info
Tetrachlorodibenzodioxin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Tetrachlorodibenzodioxin affects the expression of SLC46A1 mRNA			[22]
Regulation Mechanism				Transcription Factor Info
Thiram	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Thiram results in decreased expression of SLC46A1 mRNA			[35]
Regulation Mechanism				Transcription Factor Info
Approved Drug
Pemetrexed	5 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Pemetrexed inhibits the transportation of Methotrexate by SLC46A1			[1], [2]
Affected Drug/Substrate	Methotrexate	Modulation Type	Inhibition
Cell System	Chinese hamster ovary (CHO) cells-PCFT
DT Modulation2	Pemetrexed inhibits the activity of SLC46A1			[3]
Cell System	Chinese hamster ovary (CHO) cells-PCFT
Leucovorin	3 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Leucovorin inhibits the activity of SLC46A1			[4]
Levomefolic acid	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Levomefolic acid inhibits the activity of SLC46A1			[4]
Dronabinol	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Dronabinol inhibits the expression of SLC46A1			[5]
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 SLC46A1			[6]
Pyrimethamine	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Pyrimethamine inhibits the activity of SLC46A1			[7]
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 SLC46A1			[8]
Vitamin D	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Vitamin D increases the expression of SLC46A1			[9]
Estradiol	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Estradiol increases the expression of SLC46A1			[10]
Cisplatin	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cisplatin increases the expression of SLC46A1			[11]
Urethane	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Urethane inhibits the expression of SLC46A1			[12]
Doxorubicin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Doxorubicin inhibits the expression of SLC46A1			[13]
Sunitinib	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Sunitinib inhibits the expression of SLC46A1			[14]
Calcitriol	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Calcitriol increases the expression of SLC46A1			[15]
Cyclosporine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cyclosporine inhibits the expression of SLC46A1			[16]
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 SLC46A1			[17]
Folic Acid	9 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Folic acid modulates the activity of SLC46A1			[18]
Methotrexate	11 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Methotrexate modulates the activity of SLC46A1			[18]
Sulfasalazine	3 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Sulfasalazine inhibits the activity of SLC46A1			[19]
Bictegravir	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Bictegravir inhibits the activity of SLC46A1			[20]
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 inhibits the expression of SLC46A1			[25]
Investigative Drug
Phenylmercuric Acetate	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Phenylmercuric Acetate increases the expression of SLC46A1			[24]
Patented Pharmaceutical Agent
AM-251	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	AM-251 increases the expression of SLC46A1			[5]
Natural Product
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 expression of SLC46A1			[27]
Environmental toxicant
Polychlorinated dibenzodioxin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Polychlorinated dibenzodioxin affects the expression of SLC46A1			[22]
Acute Toxic Substance
Cadmium	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cadmium increases the expression of SLC46A1			[21]
Formaldehyde	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Formaldehyde increases the expression of SLC46A1			[23]
Carcinogen
DT Modulation1	Cadmium Chloride results in increased abundance of Cadmium which results in decreased expression of SLC46A1 mRNA			[34]
Regulation Mechanism				Transcription Factor Info
Ethyl Methanesulfonate	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Ethyl Methanesulfonate increases the expression of SLC46A1			[23]
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 SLC46A1			[26]

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