Target Information
| Target General Information | Top | |||||
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| Target ID |
T13491
(Former ID: TTDS00430)
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| Target Name |
Solute carrier family 29 member 1 (SLC29A1)
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| Synonyms |
SLC29A1; Nucleoside transporter, es-type; Nucleoside transporter 1; Equilibrative nitrobenzylmercaptopurine riboside-sensitive nucleoside transporter; Equilibrative NBMPR-sensitive nucleoside transporter; ENT1
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| Gene Name |
SLC29A1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Angina pectoris [ICD-11: BA40] | |||||
| 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.
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| UniProt ID | ||||||
| Sequence |
MTTSHQPQDRYKAVWLIFFMLGLGTLLPWNFFMTATQYFTNRLDMSQNVSLVTAELSKDA
QASAAPAAPLPERNSLSAIFNNVMTLCAMLPLLLFTYLNSFLHQRIPQSVRILGSLVAIL LVFLITAILVKVQLDALPFFVITMIKIVLINSFGAILQGSLFGLAGLLPASYTAPIMSGQ GLAGFFASVAMICAIASGSELSESAFGYFITACAVIILTIICYLGLPRLEFYRYYQQLKL EGPGEQETKLDLISKGEEPRAGKEESGVSVSNSQPTNESHSIKAILKNISVLAFSVCFIF TITIGMFPAVTVEVKSSIAGSSTWERYFIPVSCFLTFNIFDWLGRSLTAVFMWPGKDSRW LPSLVLARLVFVPLLLLCNIKPRRYLTVVFEHDAWFIFFMAAFAFSNGYLASLCMCFGPK KVKPAEAETAGAIMAFFLCLGLALGAVFSFLFRAIV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | LIDOFLAZINE | Drug Info | Approved | Angina pectoris | [2] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 8 Inhibitor drugs | + | ||||
| 1 | LIDOFLAZINE | Drug Info | [1] | |||
| 2 | 9-Benzyl-6-(4-nitro-benzylsulfanyl)-9H-purine | Drug Info | [3] | |||
| 3 | Dilazep | Drug Info | [4] | |||
| 4 | KF24345 | Drug Info | [5] | |||
| 5 | N6-CYCLOPENTYLADENOSINE | Drug Info | [6] | |||
| 6 | NBTGR | Drug Info | [7] | |||
| 7 | Nitrobenzylthioinosine | Drug Info | [8] | |||
| 8 | S6-nitrobenzyl mercaptopurine riboside | Drug Info | [9] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | [3H]nitrobenzylmercaptopurine ribonucleoside | Drug Info | [7] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Dilazep | Ligand Info | |||||
| Structure Description | Human equilibrative nucleoside transporter-1, dilazep bound | PDB:6OB7 | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [10] |
| PDB Sequence |
PQDRYKAVWL
16 IFFMLGLGTL26 LPWNFFMTAT36 QYFTNRLDMS46 QNNSLSAIFN81 NVMTLCAMLP 91 LLLFTYLNSF101 LHQRIPQSVR111 ILGSLVAILL121 VFLITAILVK131 VQLDALPFFV 141 ITMIKIVLIN151 SFGAILQGSL161 FGLAGLFPAS171 YTAAIMSGQG181 LAGFFASVAM 191 ICAIASGSEL201 SESAFGYFIT211 ACAVIILTII221 CYLGLPRLEF231 YRYYQQLKLS 281 IKAILKKISV291 LAFSVCFIFT301 ITIGMFPAVT311 VEVKSSIAGS321 STWERYFIPV 331 SCFLTFNIFD341 WLGRSLTAVF351 MWPGKDSRWL361 PSLVLARLVF371 VPLLLLCNIK 381 PRRYLTVVFE391 HDAWFIFFMA401 AFAFSNGYLA411 SLCMCFGPKK421 VKPAEAETAG 431 AIMAFFLCLG441 LALGAVFSFL451 F
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THR25
4.937
LEU26
2.522
TRP29
1.981
ASN30
2.970
MET33
2.217
THR34
2.008
THR36
2.603
ASN81
3.550
MET84
2.226
THR85
2.687
ALA88
3.530
MET89
2.611
LEU92
2.722
ASN151
3.044
GLY154
3.801
GLN158
2.299
PHE162
3.957
GLN180
3.519
ALA183
4.637
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| Ligand Name: S6-nitrobenzyl mercaptopurine riboside | Ligand Info | |||||
| Structure Description | Human equilibrative nucleoside transporter-1, S-(4-nitrobenzyl)-6-thioinosine bound, merohedrally twinned | PDB:6OB6 | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | Yes | [10] |
| PDB Sequence |
PQDRYKAVWL
16 IFFMLGLGTL26 LPWNFFMTAT36 QYFTNRLDMN74 SLSAIFNNVM84 TLCAMLPLLL 94 FTYLNSFLHQ104 RIPQSVRILG114 SLVAILLVFL124 ITAILVKVQL134 DALPFFVITM 144 IKIVLINSFG154 AILQGSLFGL164 AGLFPASYTA174 AIMSGQGLAG184 FFASVAMICA 194 IASGSELSES204 AFGYFITACA214 VIILTIICYL224 GLPRLEFYRY234 YQQSIKAILK 287 KISVLAFSVC297 FIFTITIGMF307 PAVTVEVKSS317 RYFIPVSCFL335 TFNIFDWLGR 345 SLTAVFMWPG355 KDSRWLPSLV365 LARLVFVPLL375 LLCNIKPRRY385 LTVVFEHDAW 395 FIFFMAAFAF405 SNGYLASLCM415 CFGPKKVKPA425 EAETAGAIMA435 FFLCLGLALG 445 AVFSF
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GLY24
3.614
THR25
2.741
LEU26
2.072
PRO28
3.118
TRP29
2.324
ASN30
4.484
MET33
4.028
MET89
4.334
LEU92
2.372
LEU116
4.622
ILE119
2.406
PHE123
4.290
ILE150
2.548
ASN151
3.092
GLY154
2.564
ALA155
4.193
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Similarity Proteins
Human Tissue Distribution
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Drug Resistance Mutation (DRM) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | 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. | |||||
| REF 4 | 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. | |||||
| REF 5 | 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. | |||||
| REF 6 | Inhibition of nucleoside transport proteins by C8-alkylamine-substituted purines. J Med Chem. 2005 Jan 13;48(1):321-9. | |||||
| REF 7 | 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). | |||||
| REF 8 | The role of human nucleoside transporters in uptake of 3'-deoxy-3'-fluorothymidine. Mol Pharmacol. 2008 Nov;74(5):1372-80. | |||||
| REF 9 | 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. | |||||
| REF 10 | Structures of human ENT1 in complex with adenosine reuptake inhibitors. Nat Struct Mol Biol. 2019 Jul;26(7):599-606. | |||||
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