Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTMHCGA)

• DTT Name: Solute carrier family 47 member 1 (SLC47A1)
• Synonyms: hMATE-1; Multidrug and toxin extrusion protein 1; MATE1; MATE-1
• Gene Name: SLC47A1
• DTT Type: Successful target; [1]
• UniProt ID: S47A1_HUMAN
• TTD ID: T39676
• Sequence:
  MEAPEEPAPVRGGPEATLEVRGSRCLRLSAFREELRALLVLAGPAFLVQLMVFLISFISS
  VFCGHLGKLELDAVTLAIAVINVTGVSVGFGLSSACDTLISQTYGSQNLKHVGVILQRSA
  LVLLLCCFPCWALFLNTQHILLLFRQDPDVSRLTQTYVTIFIPALPATFLYMLQVKYLLN
  QGIVLPQIVTGVAANLVNALANYLFLHQLHLGVIGSALANLISQYTLALLLFLYILGKKL
  HQATWGGWSLECLQDWASFLRLAIPSMLMLCMEWWAYEVGSFLSGILGMVELGAQSIVYE
  LAIIVYMVPAGFSVAASVRVGNALGAGDMEQARKSSTVSLLITVLFAVAFSVLLLSCKDH
  VGYIFTTDRDIINLVAQVVPIYAVSHLFEALACTSGGVLRGSGNQKVGAIVNTIGYYVVG
  LPIGIALMFATTLGVMGLWSGIIICTVFQAVCFLGFIIQLNWKKACQQAQVHANLKVNNV
  PRSGNSALPQDPLHPGCPENLEGILTNDVGKTGEPQSDQQMRQEEPLPEHPQDGAKLSRK
  QLVLRRGLLLLGVFLILLVGILVRFYVRIQ
• Function: Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
• Reactome Pathway: Transport of bile salts and organic acids, metal ions and amine compounds (R-HSA-425366)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metformin	DM89QE1	Colorectal carcinoma		Approved	[1]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[1]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Multidrug and toxin extrusion protein 1 (SLC47A1) DTP Info
• Gene Name: SLC47A1

15 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aciclovir	DMYLOVR	Genital herpes	1A94	Approved	[2]
Auranofin	DMWE2N4	Inflammatory arthritis	FA2Z	Approved	[3]
Cephalexin	DMD5JU8	Acute otitis media	AB00	Approved	[4]
Chloroquine	DMSI5CB	Malaria	1F40-1F45	Approved	[5]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[2]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[6]
Emtricitabine	DMBMUWZ	Hepatitis virus infection	1E50-1E51	Approved	[7]
Enoxacin	DMYTE6L	Acute gonococcal cervicitis		Approved	[8]
Estrone sulfate	DMVBIZL	Atrophic vaginitis	GA30.2	Approved	[2]
Ganciclovir	DM1MBYQ	Cytomegalovirus infection	1D82	Approved	[2]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[9]
Metformin	DM89QE1	Colorectal carcinoma		Approved	[10]
Procainamide	DMNMXR8	Ventricular arrhythmias	BC71	Approved	[2]
Pyrimethamine	DM5X7VY	Malaria	1F40-1F45	Approved	[11]
Topotecan	DMP6G8T	Central nervous system neoplasm		Approved	[2]

2 Preclinical Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mephenoxalone	DMX4IS3	N. A.	N. A.	Preclinical	[12]
N-methylpyridinium	DMVUKEW	N. A.	N. A.	Preclinical	[2]

2 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
paraquat	DMR8O3X	Discovery agent	N.A.	Investigative	[13]
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[14]

References

• [1] Molecular cloning, functional characterization and tissue distribution of rat H+/organic cation antiporter MATE1. Pharm Res. 2006 Aug;23(8):1696-701.
• [2] Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71.
• [3] Selection and characterization of a human ovarian cancer cell line resistant to auranofin. Oncotarget. 2017 Oct 9;8(56):96062-96078.
• [4] Reduced renal clearance of a zwitterionic substrate cephalexin in MATE1-deficient mice. J Pharmacol Exp Ther. 2010 Aug;334(2):651-6.
• [5] Molecular mechanism of renal tubular secretion of the antimalarial drug chloroquine. Antimicrob Agents Chemother. 2011 Jul;55(7):3091-8.
• [6] FDA Drug Development and Drug Interactions
• [7] Emtricitabine is a substrate of MATE1 but not of OCT1, OCT2, P-gp, BCRP or MRP2 transporters. Xenobiotica. 2017 Jan;47(1):77-85.
• [8] Functional characterization of multidrug and toxin extrusion protein 1 as a facilitative transporter for fluoroquinolones. J Pharmacol Exp Ther. 2009 Feb;328(2):628-34.
• [9] Abemaciclib Inhibits Renal Tubular Secretion Without Changing Glomerular Filtration Rate. Clin Pharmacol Ther. 2019 May;105(5):1187-1195.
• [10] Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2 (SLC22A2), and single nucleotide polymorphisms. Am J Physiol Renal Physiol. 2010 Apr;298(4):F997-F1005.
• [11] Expression of Organic Anion Transporter 1 or 3 in Human Kidney Proximal Tubule Cells Reduces Cisplatin Sensitivity. Drug Metab Dispos. 2018 May;46(5):592-599.
• [12] Preclinical and clinical evidence for the collaborative transport and renal secretion of an oxazolidinone antibiotic by organic anion transporter 3 (OAT3/SLC22A8) and multidrug and toxin extrusion protein 1 (MATE1/SLC47A1). J Pharmacol Exp Ther. 2010 Sep 1;334(3):936-44.
• [13] Genetic variants in multidrug and toxic compound extrusion-1, hMATE1, alter transport function. Pharmacogenomics J. 2009 Apr;9(2):127-36.
• [14] A human transporter protein that mediates the final excretion step for toxic organic cations. Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):17923-8.