Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZX0U5Q)

• DOT Name: Multidrug and toxin extrusion protein 1 (SLC47A1)
• Synonyms: MATE-1; hMATE-1; Solute carrier family 47 member 1
• Gene Name: SLC47A1
• UniProt ID: S47A1_HUMAN
• Pfam ID: PF01554
• Sequence:
  MEAPEEPAPVRGGPEATLEVRGSRCLRLSAFREELRALLVLAGPAFLVQLMVFLISFISS
  VFCGHLGKLELDAVTLAIAVINVTGVSVGFGLSSACDTLISQTYGSQNLKHVGVILQRSA
  LVLLLCCFPCWALFLNTQHILLLFRQDPDVSRLTQTYVTIFIPALPATFLYMLQVKYLLN
  QGIVLPQIVTGVAANLVNALANYLFLHQLHLGVIGSALANLISQYTLALLLFLYILGKKL
  HQATWGGWSLECLQDWASFLRLAIPSMLMLCMEWWAYEVGSFLSGILGMVELGAQSIVYE
  LAIIVYMVPAGFSVAASVRVGNALGAGDMEQARKSSTVSLLITVLFAVAFSVLLLSCKDH
  VGYIFTTDRDIINLVAQVVPIYAVSHLFEALACTSGGVLRGSGNQKVGAIVNTIGYYVVG
  LPIGIALMFATTLGVMGLWSGIIICTVFQAVCFLGFIIQLNWKKACQQAQVHANLKVNNV
  PRSGNSALPQDPLHPGCPENLEGILTNDVGKTGEPQSDQQMRQEEPLPEHPQDGAKLSRK
  QLVLRRGLLLLGVFLILLVGILVRFYVRIQ
• Function: Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively. Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate. May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable).
• Tissue Specificity: Widely expressed. The highest expression is found in adrenal gland, and to a lower extent in liver, skeletal muscle and kidney. In testis, primarily localized throughout the adluminal compartment of the seminiferous tubules with expression at the peritubular myoid cells and Leydig cells .
• Reactome Pathway: Transport of bile salts and organic acids, metal ions and amine compounds (R-HSA-425366)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Multidrug and toxin extrusion protein 1 (SLC47A1) affects the response to substance of Fluorouracil.	[26]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
[14C]TEA	DM6SFYH	Investigative	Multidrug and toxin extrusion protein 1 (SLC47A1) decreases the uptake of [14C]TEA.	[27]

25 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[10]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[11]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[12]
Mebendazole	DMO14SG	Approved	Mebendazole decreases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[13]
Cimetidine	DMH61ZB	Approved	Cimetidine decreases the activity of Multidrug and toxin extrusion protein 1 (SLC47A1).	[14]
Imipramine	DM2NUH3	Approved	Imipramine decreases the activity of Multidrug and toxin extrusion protein 1 (SLC47A1).	[14]
Quinidine	DMLPICK	Approved	Quinidine decreases the activity of Multidrug and toxin extrusion protein 1 (SLC47A1).	[14]
Amiloride	DMRTSGP	Approved	Amiloride decreases the activity of Multidrug and toxin extrusion protein 1 (SLC47A1).	[14]
Pyrimethamine	DM5X7VY	Approved	Pyrimethamine decreases the activity of Multidrug and toxin extrusion protein 1 (SLC47A1).	[15]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[17]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl increases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[18]
Verapamil	DMA7PEW	Phase 2/3 Trial	Verapamil decreases the activity of Multidrug and toxin extrusion protein 1 (SLC47A1).	[19]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[24]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Multidrug and toxin extrusion protein 1 (SLC47A1).	[25]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Multidrug and toxin extrusion protein 1 (SLC47A1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Multidrug and toxin extrusion protein 1 (SLC47A1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Multidrug and toxin extrusion protein 1 (SLC47A1).	[23]

References

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