Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Solute carrier family 29 member 1 (SLC29A1)
• Synonyms: SLC29A1; Nucleoside transporter, es-type; Nucleoside transporter 1; Equilibrative nitrobenzylmercaptopurine riboside-sensitive nucleoside transporter; Equilibrative NBMPR-sensitive nucleoside transporter; ENT1
• Gene Name: SLC29A1
• DTT Type: Successful target; [1]
• UniProt ID: S29A1_HUMAN
• TTD ID: T13491
• Sequence:
  MTTSHQPQDRYKAVWLIFFMLGLGTLLPWNFFMTATQYFTNRLDMSQNVSLVTAELSKDA
  QASAAPAAPLPERNSLSAIFNNVMTLCAMLPLLLFTYLNSFLHQRIPQSVRILGSLVAIL
  LVFLITAILVKVQLDALPFFVITMIKIVLINSFGAILQGSLFGLAGLLPASYTAPIMSGQ
  GLAGFFASVAMICAIASGSELSESAFGYFITACAVIILTIICYLGLPRLEFYRYYQQLKL
  EGPGEQETKLDLISKGEEPRAGKEESGVSVSNSQPTNESHSIKAILKNISVLAFSVCFIF
  TITIGMFPAVTVEVKSSIAGSSTWERYFIPVSCFLTFNIFDWLGRSLTAVFMWPGKDSRW
  LPSLVLARLVFVPLLLLCNIKPRRYLTVVFEHDAWFIFFMAAFAFSNGYLASLCMCFGPK
  KVKPAEAETAGAIMAFFLCLGLALGAVFSFLFRAIV
• Function: Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (nbmpr) and is sodium-independent.
• KEGG Pathway: Alcoholism (hsa05034)
• Reactome Pathway:
  Azathioprine ADME (R-HSA-9748787)
  Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane (R-HSA-83936)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LIDOFLAZINE	DMV23GL	Angina pectoris	BA40	Approved	[1]

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
6-(4-Nitro-benzylsulfanyl)-9-phenethyl-9H-purine	DMPL5XV	Discovery agent	N.A.	Investigative	[2]
9-Benzyl-6-(4-nitro-benzylsulfanyl)-9H-purine	DMNY5P1	Discovery agent	N.A.	Investigative	[2]
Dilazep	DMOD5Y0	Discovery agent	N.A.	Investigative	[3]
KF24345	DMK6SMW	Discovery agent	N.A.	Investigative	[4]
N6-CYCLOPENTYLADENOSINE	DMD6AJO	Discovery agent	N.A.	Investigative	[5]
NBTGR	DMVF420	Discovery agent	N.A.	Investigative	[6]
Nitrobenzylthioinosine	DM7F3RY	Discovery agent	N.A.	Investigative	[7]
S6-nitrobenzyl mercaptopurine riboside	DMIKJNL	Discovery agent	N.A.	Investigative	[8]
[3H]nitrobenzylmercaptopurine ribonucleoside	DM5TDFQ	Discovery agent	N.A.	Investigative	[6]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Equilibrative nucleoside transporter 1 (SLC29A1) DTP Info
• Gene Name: SLC29A1

8 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Adenosine	DMM2NSK	Paroxysmal supraventricular tachycardia	BC81.Z	Approved	[9]
Clofarabine	DMCVJ86	Acute lymphoblastic leukaemia	2A85	Approved	[10]
Cytarabine	DMZD5QR	Acute lymphoblastic leukaemia	2A85	Approved	[11]
Entecavir	DM7VTQO	Hepatitis B virus infection	1E51.0	Approved	[12]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[13]
Mercaptopurine	DMTM2IK	Acute lymphoblastic leukaemia	2A85	Approved	[14]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[15]
Trifluridine	DMG2YBD	Herpetic keratitis	1F00.10	Approved	[16]

1 Discontinued Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tecadenoson	DM9T6MS	Atrial fibrillation	BC81.3	Discontinued in Phase 3	[17]

References

• [1] Synthesis, flow cytometric evaluation, and identification of highly potent dipyridamole analogues as equilibrative nucleoside transporter 1 inhibit... J Med Chem. 2007 Aug 9;50(16):3906-20.
• [2] Inhibition of nucleoside transport by new analogues of 4-nitrobenzylthioinosine: replacement of the ribose moiety by substituted benzyl groups. J Med Chem. 2004 Oct 21;47(22):5441-50.
• [3] Residues Met89 and Ser160 in the human equilibrative nucleoside transporter 1 affect its affinity for adenosine, guanosine, S6-(4-nitrobenzyl)-merc... Mol Pharmacol. 2005 Mar;67(3):837-44.
• [4] Interaction of the novel adenosine uptake inhibitor 3-[1-(6,7-diethoxy-2-morpholinoquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H,3H)-quinazol... J Pharmacol Exp Ther. 2004 Mar;308(3):1083-93.
• [5] Inhibition of nucleoside transport proteins by C8-alkylamine-substituted purines. J Med Chem. 2005 Jan 13;48(1):321-9.
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1117).
• [7] The role of human nucleoside transporters in uptake of 3'-deoxy-3'-fluorothymidine. Mol Pharmacol. 2008 Nov;74(5):1372-80.
• [8] Synthesis and biological evaluation of phloridzin analogs as human concentrative nucleoside transporter 3 (hCNT3) inhibitors. Bioorg Med Chem Lett. 2009 Feb 1;19(3):917-21.
• [9] Nitric oxide reduces adenosine transporter ENT1 gene (SLC29A1) promoter activity in human fetal endothelium from gestational diabetes. J Cell Physiol. 2006 Aug;208(2):451-60.
• [10] Cytarabine-resistant leukemia cells are moderately sensitive to clofarabine in vitro. Anticancer Res. 2014 Apr;34(4):1657-62.
• [11] FLT3 is implicated in cytarabine transport by human equilibrative nucleoside transporter 1 in pediatric acute leukemia. Oncotarget. 2016 Aug 2;7(31):49786-49799.
• [12] Multiple SLC and ABC Transporters Contribute to the Placental Transfer of Entecavir. Drug Metab Dispos. 2017 Mar;45(3):269-278.
• [13] Human equilibrative nucleoside transporter 1, as a predictor of 5-fluorouracil resistance in human pancreatic cancer. Anticancer Res. 2007 Jul-Aug;27(4B):2241-9.
• [14] PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA2040)
• [15] Effects of dipyridamole coadministration on the pharmacokinetics of ribavirin in healthy volunteers. Drug Metab Pharmacokinet. 2013;28(5):406-10.
• [16] Lonsurf, INN-trifluridine/tipiracil.
• [17] Transport of A1 adenosine receptor agonist tecadenoson by human and mouse nucleoside transporters: evidence for blood-brain barrier transport by murine equilibrative nucleoside transporter 1 mENT1. Drug Metab Dispos. 2013 Apr;41(4):916-22.