Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID	DTD0023 Transporter Info
Gene Name	SLC22A5
Transporter Name	Organic cation/carnitine transporter 2
Gene ID	6584
UniProt ID	O76082

Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)
Chemical Compound
DT Modulation1	Ofloxacin inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[34]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Valproic Acid results in decreased methylation of SLC22A5 gene			[55]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Cisplatin co-treated with jinfukang results in decreased expression of SLC22A5 mRNA			[45]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Verapamil results in decreased activity of SLC22A5 protein			[11]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Carnitine inhibits the reaction SLC22A5 protein results in increased abundance of Doxorubicin			[39]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Doxorubicin co-treated with Carnitine results in increased expression of SLC22A5 mRNA			[41]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	Metformin inhibits the reaction SLC22A5 protein results in increased abundance of Doxorubicin			[39]
Regulation Mechanism				Transcription Factor Info
DT Modulation4	SLC22A5 protein results in increased abundance of Doxorubicin			[39]
Regulation Mechanism				Transcription Factor Info
DT Modulation1	Progesterone results in increased expression of SLC22A5 mRNA			[53]
Regulation Mechanism				Transcription Factor Info
3-(2,2,2-trimethylhydrazine)propionate	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC22A5 protein results in increased uptake of 3-(2,2,2-trimethylhydrazine)propionate			[29]
Regulation Mechanism				Transcription Factor Info
afimoxifene	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	afimoxifene inhibits the reaction Estrogens results in increased expression of SLC22A5 mRNA			[30]
Regulation Mechanism				Transcription Factor Info
Amiodarone	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Amiodarone inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[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 SLC22A5 mRNA			[32]
Regulation Mechanism				Transcription Factor Info
Arsenic Trioxide	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC22A5 protein results in decreased susceptibility to Arsenic Trioxide			[33]
Regulation Mechanism				Transcription Factor Info
Betaine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Betaine inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[34]
Regulation Mechanism				Transcription Factor Info
beta-lapachone	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	beta-lapachone results in increased expression of SLC22A5 mRNA			[35]
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 abundance of Cadmium which results in increased expression of SLC22A5 mRNA			[36]
Regulation Mechanism				Transcription Factor Info
Carmustine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC22A5 mRNA affects the susceptibility to Carmustine			[37]
Regulation Mechanism				Transcription Factor Info
Carnitine	27 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Amiodarone inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Atorvastatin inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	Betaine inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[34]
Regulation Mechanism				Transcription Factor Info
DT Modulation4	Carnitine binds to SLC22A5 protein			[38]
Regulation Mechanism				Transcription Factor Info
DT Modulation5	Carnitine inhibits the reaction SLC22A5 protein results in increased abundance of Doxorubicin			[39]
Regulation Mechanism				Transcription Factor Info
DT Modulation6	Carnitine inhibits the reaction SLC22A5 protein results in increased transport of pivaloylcarnitine			[38]
Regulation Mechanism				Transcription Factor Info
DT Modulation7	Carnitine results in decreased expression of SLC22A5 mRNA			[40]
Regulation Mechanism				Transcription Factor Info
DT Modulation8	Carnitine results in decreased expression of SLC22A5 protein			[40]
Regulation Mechanism				Transcription Factor Info
DT Modulation9	Choline inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[34]
Regulation Mechanism				Transcription Factor Info
DT Modulation10	Clozapine inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[40]
Regulation Mechanism				Transcription Factor Info
DT Modulation11	Doxorubicin co-treated with Carnitine results in increased expression of SLC22A5 mRNA			[41]
Regulation Mechanism				Transcription Factor Info
DT Modulation12	grepafloxacin affects the reaction SLC22A5 protein results in increased uptake of Carnitine			[34]
Regulation Mechanism				Transcription Factor Info
DT Modulation13	Ipratropium inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
DT Modulation14	Lidocaine inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
DT Modulation15	Nifedipine inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
DT Modulation16	Ofloxacin inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[34]
Regulation Mechanism				Transcription Factor Info
DT Modulation17	Olanzapine inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine analog			[42]
Regulation Mechanism				Transcription Factor Info
DT Modulation18	pivaloylcarnitine inhibits the reaction SLC22A5 protein results in increased transport of Carnitine			[38]
Regulation Mechanism				Transcription Factor Info
DT Modulation19	Propranolol inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
DT Modulation20	Quetiapine Fumarate inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[40]
Regulation Mechanism				Transcription Factor Info
DT Modulation21	SLC22A5 protein affects the uptake of Carnitine			[11]
Regulation Mechanism				Transcription Factor Info
DT Modulation22	SLC22A5 protein results in increased transport of Carnitine			[38]
Regulation Mechanism				Transcription Factor Info
DT Modulation23	SLC22A5 protein results in increased uptake of Carnitine			[34]
Regulation Mechanism				Transcription Factor Info
DT Modulation24	SLC22A5 protein results in increased uptake of Carnitine analog			[42]
Regulation Mechanism				Transcription Factor Info
DT Modulation25	Spironolactone inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
DT Modulation26	talinolol inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
DT Modulation27	ziprasidone inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[40]
Regulation Mechanism				Transcription Factor Info
Catechin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Catechin co-treated with Grape Seed Proanthocyanidins results in increased expression of SLC22A5 mRNA			[43]
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 SLC22A5 gene			[44]
Regulation Mechanism				Transcription Factor Info
Choline	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Choline inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[34]
Regulation Mechanism				Transcription Factor Info
Clozapine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Clozapine inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[40]
Regulation Mechanism				Transcription Factor Info
di-n-butylphosphoric acid	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	di-n-butylphosphoric acid affects the expression of SLC22A5 mRNA			[46]
Regulation Mechanism				Transcription Factor Info
enilconazole	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	enilconazole results in decreased expression of SLC22A5 mRNA			[47]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	enilconazole results in decreased expression of SLC22A5 protein			[47]
Regulation Mechanism				Transcription Factor Info
Estrogens	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	afimoxifene inhibits the reaction Estrogens results in increased expression of SLC22A5 mRNA			[30]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	Estrogens results in increased expression of SLC22A5 mRNA			[30]
Regulation Mechanism				Transcription Factor Info
grepafloxacin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	grepafloxacin affects the reaction SLC22A5 protein results in increased uptake of Carnitine			[34]
Regulation Mechanism				Transcription Factor Info
Hydroxyurea	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC22A5 protein results in increased uptake of Hydroxyurea			[48]
Regulation Mechanism				Transcription Factor Info
Ipratropium	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Ipratropium inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
Lidocaine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Lidocaine inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
mono-(2-ethylhexyl)phthalate	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	mono-(2-ethylhexyl)phthalate results in increased expression of SLC22A5 mRNA			[49]
Regulation Mechanism				Transcription Factor Info
Nifedipine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Nifedipine inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
Olanzapine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Olanzapine inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine analog			[42]
Regulation Mechanism				Transcription Factor Info
Oxaliplatin	3 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC22A5 protein results in increased import of Oxaliplatin			[50]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	SLC22A5 protein results in increased susceptibility to Oxaliplatin			[50]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	tetrahydropalmatine inhibits the reaction SLC22A5 protein results in increased import of Oxaliplatin			[50]
Regulation Mechanism				Transcription Factor Info
Ozone	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Air Pollutants results in increased abundance of Ozone which affects the expression of SLC22A5 mRNA			[51]
Regulation Mechanism				Transcription Factor Info
pivaloylcarnitine	5 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Carnitine inhibits the reaction SLC22A5 protein results in increased transport of pivaloylcarnitine			[38]
Regulation Mechanism				Transcription Factor Info
DT Modulation2	pivaloylcarnitine binds to SLC22A5 protein			[38]
Regulation Mechanism				Transcription Factor Info
DT Modulation3	pivaloylcarnitine inhibits the reaction SLC22A5 protein results in increased transport of Carnitine			[38]
Regulation Mechanism				Transcription Factor Info
DT Modulation4	SLC22A5 protein results in increased transport of pivaloylcarnitine			[38]
Regulation Mechanism				Transcription Factor Info
DT Modulation5	SLC22A5 protein results in increased uptake of pivaloylcarnitine			[52]
Regulation Mechanism				Transcription Factor Info
Propranolol	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Propranolol inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
Quetiapine Fumarate	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Quetiapine Fumarate inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[40]
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 decreased expression of SLC22A5 mRNA			[54]
Regulation Mechanism				Transcription Factor Info
Spironolactone	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Spironolactone inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
talinolol	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	talinolol inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
Temozolomide	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC22A5 mRNA affects the susceptibility to Temozolomide			[37]
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 SLC22A5 mRNA			[25]
Regulation Mechanism				Transcription Factor Info
tetrahydropalmatine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	tetrahydropalmatine inhibits the reaction SLC22A5 protein results in increased import of Oxaliplatin			[50]
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 SLC22A5 mRNA			[54]
Regulation Mechanism				Transcription Factor Info
valproylcarnitine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	SLC22A5 protein results in increased uptake of valproylcarnitine			[52]
Regulation Mechanism				Transcription Factor Info
ziprasidone	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	ziprasidone inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[40]
Regulation Mechanism				Transcription Factor Info
Approved Drug
Cefepime	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cefepime inhibits the transportation of L-carnitine by SLC22A5 (IC50 = 1700 microM)			[1]
Affected Drug/Substrate	L-carnitine	Modulation Type	Inhibition
Cell System	Human cervical cancer cell line (Hela)-OCTN2
DT Modulation2	Cefepime inhibits the activity of SLC22A5			[1]
Nicotine polacrilex	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Nicotine inhibits the transportation of L-Carnitine by SLC22A5			[2]
Affected Drug/Substrate	L-Carnitine	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-OCTN2
DT Modulation2	Nicotine inhibits the transportation of Tetraethylammonium by SLC22A5			[4]
Affected Drug/Substrate	Tetraethylammonium	Modulation Type	Inhibition
Cell System	Human cervical cancer cell line (Hela)-OCTN2
L-carnitine	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	L-carnitine inhibits the transportation of L-Carnitine by SLC22A5			[3]
Affected Drug/Substrate	L-Carnitine	Modulation Type	Inhibition
Cell System	Oocytes-OCTN2
DT Modulation2	L-carnitine inhibits the transportation of Carnitine by SLC22A5			[5]
Affected Drug/Substrate	Carnitine	Modulation Type	Inhibition
Cefoselis	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cefoselis inhibits the transportation of L-carnitine by SLC22A5 (IC50 = 6400 microM)			[1]
Affected Drug/Substrate	L-carnitine	Modulation Type	Inhibition
Cell System	Human cervical cancer cell line (Hela)-OCTN2
Emetine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Emetine inhibits the transportation of L-carnitine by SLC22A5 (IC50 = 4.2 microM)			[6]
Affected Drug/Substrate	L-carnitine	Modulation Type	Inhibition
Cell System	Oocytes-OCTN2
Linagliptin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Linagliptin inhibits the transportation of Ergothioneine by SLC22A5			[7]
Affected Drug/Substrate	Ergothioneine	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-OCTN2
Quinine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Quinine inhibits the transportation of Ergothioneine by SLC22A5			[7]
Affected Drug/Substrate	Ergothioneine	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-OCTN2
Aldosterone	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Aldosterone inhibits the transportation of L-Carnitine by SLC22A5			[2]
Affected Drug/Substrate	L-Carnitine	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-OCTN2
Cefsulodin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cefsulodin inhibits the transportation of L-Carnitine by SLC22A5			[2]
Affected Drug/Substrate	L-Carnitine	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-OCTN2
Lomefloxacin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Lomefloxacin inhibits the transportation of L-Carnitine by SLC22A5			[2]
Affected Drug/Substrate	L-Carnitine	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-OCTN2
Ofloxacin	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Ofloxacin inhibits the transportation of L-Carnitine by SLC22A5			[2]
Affected Drug/Substrate	L-Carnitine	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-OCTN2
Pyrilamide	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Pyrilamide inhibits the transportation of L-Carnitine by SLC22A5			[2]
Affected Drug/Substrate	L-Carnitine	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-OCTN2
Valproic Acid	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Valproic Acid inhibits the transportation of L-Carnitine by SLC22A5			[2]
Affected Drug/Substrate	L-Carnitine	Modulation Type	Inhibition
Cell System	Human embryonic kidney 293 cells (HEK293)-OCTN2
Methamphetamine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Methamphetamine inhibits the transportation of Tetraethylammonium by SLC22A5			[4]
Affected Drug/Substrate	Tetraethylammonium	Modulation Type	Inhibition
Cell System	Human cervical cancer cell line (Hela)-OCTN2
Carbamazepine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Carbamazepine increases the expression of SLC22A5			[8]
Regulation Mechanism	via enhancement of Nuclear receptor subfamily 1 group I member 2 (NR1I2)			Transcription Factor Info
Cell System	Human liver samples
Cisplatin	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cisplatin inhibits the expression of SLC22A5			[9]
Regulation Mechanism	via the inhibition of Peroxisome proliferator-activated receptor alpha (PPARA)			Transcription Factor Info
Cell System	FVB wild-type mice
Raloxifene Hydrochloride	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Raloxifene Hydrochloride affects the expression of SLC22A5			[10]
Verapamil	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Verapamil inhibits the activity of SLC22A5			[11]
Cyclosporine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cyclosporine increases the expression of SLC22A5			[12]
Tretinoin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Tretinoin increases the expression of SLC22A5			[13]
Zidovudine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Zidovudine increases the expression of SLC22A5			[14]
Rosiglitazone	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Rosiglitazone increases the expression of SLC22A5			[15]
Vorinostat	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Vorinostat inhibits the expression of SLC22A5			[16]
Decitabine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Decitabine increases the expression of SLC22A5			[17]
Urethane	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Urethane inhibits the expression of SLC22A5			[18]
Doxorubicin	5 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Doxorubicin inhibits the expression of SLC22A5			[19]
Arsenic	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Arsenic affects the expression of SLC22A5			[20]
Sunitinib	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Sunitinib inhibits the expression of SLC22A5			[21]
Estradiol	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Estradiol increases the expression of SLC22A5			[22]
Progesterone	2 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Progesterone inhibits the activity of SLC22A5			[23]
Atorvastatin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Atorvastatin inhibits the reaction SLC22A5 protein results in increased uptake of Carnitine			[31]
Regulation Mechanism				Transcription Factor Info
Metformin	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Metformin inhibits the reaction SLC22A5 protein results in increased abundance of Doxorubicin			[39]
Regulation Mechanism				Transcription Factor Info
Drug in Phase 2 Trial
Genistein	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Genistein increases the expression of SLC22A5			[26]
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 SLC22A5			[24]
Drug Withdrawn
Cephaloridine	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cephaloridine inhibits the transportation of L-carnitine by SLC22A5 (IC50 = 230 microM)			[1]
Affected Drug/Substrate	L-carnitine	Modulation Type	Inhibition
Cell System	Human cervical cancer cell line (Hela)-OCTN2
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 affects the expression of SLC22A5			[28]
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 SLC22A5			[25]
Carcinogen
DT Modulation1	Arsenic results in increased methylation of SLC22A5 gene			[20]
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 SLC22A5			[27]
Cadmium	1 DT Activity Modulations Related to This Exogenous Factor		Click to Show/Hide the Full List
DT Modulation1	Cadmium Chloride results in increased abundance of Cadmium which results in increased expression of SLC22A5 mRNA			[36]
Regulation Mechanism				Transcription Factor Info

References
1	beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem. 2000 Jan 21;275(3):1699-707.
2	Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84.
3	Molecular identification of a novel carnitine transporter specific to human testis. Insights into the mechanism of carnitine recognition. J Biol Chem. 2002 Sep 27;277(39):36262-71.
4	cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun. 1998 May 29;246(3):589-95.
5	Pharmacokinetics and hepatic uptake of eltrombopag, a novel platelet-increasing agent. Drug Metab Dispos. 2011 Jun;39(6):1088-96.
6	Functional and pharmacological characterization of human Na(+)-carnitine cotransporter hOCTN2. Am J Physiol Renal Physiol. 2000 Sep;279(3):F584-91.
7	Evaluation and prediction of potential drug-drug interactions of linagliptin using in vitro cell culture methods. Drug Metab Dispos. 2013 Jan;41(1):149-58.
8	Transcriptional profiling of genes induced in the livers of patients treated with carbamazepine. Clin Pharmacol Ther. 2006 Nov;80(5):440-456.
9	Cisplatin-induced downregulation of OCTN2 affects carnitine wasting. Clin Cancer Res. 2010 Oct 1;16(19):4789-99.
10	Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72.
11	Expression, localization, and function of the carnitine transporter octn2 (slc22a5) in human placenta. Drug Metab Dispos. 2005 Jan;33(1):31-7.
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	Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
14	Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23.
15	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.
16	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.
17	Multiple drug transporters mediate the placental transport of sulpiride. Arch Toxicol. 2017 Dec;91(12):3873-3884.
18	Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
19	Bringing in vitro analysis closer to in vivo: Studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
20	Inorganic Arsenic as an Endocrine Disruptor: Modulation of the Glucocorticoid Receptor Pathway in Placental Cells via CpG Methylation. Chem Res Toxicol. 2019 Mar 18;32(3):493-499.
21	Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761.
22	17 beta-Estradiol Activates HSF1 via MAPK Signaling in ER alpha-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533.
23	Maternal Plasma l-Carnitine Reduction During Pregnancy Is Mainly Attributed to OCTN2-Mediated Placental Uptake and Does Not Result in Maternal Hepatic Fatty Acid -Oxidation Decline. Drug Metab Dispos. 2019 Jun;47(6):582-591.
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25	Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711.
26	Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
27	Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
28	Assessment of the impact of aerosol from a potential modified risk tobacco product compared with cigarette smoke on human organotypic oral epithelial cultures under different exposure regimens. Food Chem Toxicol. 2018 May;115:148-169.
29	The carnitine transporter SLC22A5 is not a general drug transporter, but it efficiently translocates mildronate. Drug Metab Dispos. 2009;37(2):330-7.
30	High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011;108(5):2058-63.
31	Selective regulation of cardiac organic cation transporter novel type 2 (OCTN2) in dilated cardiomyopathy. Am J Pathol. 2011 Jun;178(6):2547-59.
32	Integration of transcriptomic, proteomic and metabolomic data to reveal the biological mechanisms of AAI injury in renal epithelial cells. Toxicol In Vitro. 2021;70:105054.
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35	Lapachone induces ferroptosis of colorectal cancer cells via NCOA4-mediated ferritinophagy by activating JNK pathway. Chem Biol Interact. 2024;389:110866.
36	Cadmium acute exposure induces metabolic and transcriptomic perturbations in human mature adipocytes. Toxicology. 2022;470:153153.
37	Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006;24(2):274-87.
38	Interaction between pivaloylcarnitine and L-carnitine transport into L6 cells overexpressing hOCTN2. Chem Biol Interact. 2009;180(3):472-7.
39	Inhibition of multiple uptake transporters in cardiomyocytes/mitochondria alleviates doxorubicin-induced cardiotoxicity. Chem Biol Interact. 2023;382:110627.
40	Clozapine-induced reduction of l-carnitine reabsorption via inhibition/down-regulation of renal carnitine/organic cation transporter 2 contributes to liver lipid metabolic disorder in mice. Toxicol Appl Pharmacol. 2019;363:47-56.
41	Effects of doxorubicin-containing chemotherapy and a combination with L-carnitine on oxidative metabolism in patients with non-Hodgkin lymphoma. J Cancer Res Clin Oncol. 2006;132(2):121-8.
42	Up-regulation of hepatic fatty acid transporters and inhibition/down-regulation of hepatic OCTN2 contribute to olanzapine-induced liver steatosis. Toxicol Lett. 2019 Nov;316:183-193.
43	Dietary flavanols modulate the transcription of genes associated with cardiovascular pathology without changes in their DNA methylation state. PLoS One. 2014;9(4):e95527.
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45	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
46	Association between Organophosphate Ester Exposure and Insulin Resistance with Glycometabolic Disorders among Older Chinese Adults 60-69 Years of Age: Evidence from the China BAPE Study. Environ Health Perspect. 2023;131(4):47009.
47	Cross-generational effects of maternal exposure to imazalil on anaerobic components and carnitine absorption associated with OCTN2 expression in mice. Chemosphere. 2022;308(Pt 3):136542.
48	Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56.
49	Exposure to the phthalate metabolite MEHP impacts survival and growth of human ovarian follicles in vitro. Toxicology. 2024;505:153815.
50	L-tetrahydropalmatine reduces oxaliplatin accumulation in the dorsal root ganglion and mitochondria through selectively inhibiting the transporter-mediated uptake thereby attenuates peripheral neurotoxicity. Toxicology. 2021;459:152853.
51	Ozone exposure and blood transcriptome: A randomized, controlled, crossover trial among healthy adults. Environ Int. 2022;163:107242.
52	Role of Na+/L-carnitine transporter (OCTN2) in renal handling of pivaloylcarnitine and valproylcarnitine formed during pivalic acid-containing prodrugs and valproic acid treatment. Drug Metab Pharmacokinet. 2008;23(4):293-303.
53	Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
54	High-Throughput Transcriptomics of Nontumorigenic Breast Cells Exposed to Environmentally Relevant Chemicals. Environ Health Perspect. 2024;132(4):47002.
55	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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