SLC29A1

Summary

SLC29A1 (solute carrier family 29 member 1 (Augustine blood group), HGNC:11003) is a protein-coding gene on chromosome 6p21.1, encoding Equilibrative nucleoside transporter 1 (Q99808). Uniporter involved in the facilitative transport of nucleosides and nucleobases, and contributes to maintaining their cellular homeostasis. In precision oncology, SLC29A1 Overexpression confers sensitivity to Gemcitabine in Pancreatic Adenocarcinoma (CIViC Level B).

This gene is a member of the equilibrative nucleoside transporter family. The gene encodes a transmembrane glycoprotein that localizes to the plasma and mitochondrial membranes and mediates the cellular uptake of nucleosides from the surrounding medium. The protein is categorized as an equilibrative (as opposed to concentrative) transporter that is sensitive to inhibition by nitrobenzylthioinosine (NBMPR). Nucleoside transporters are required for nucleotide synthesis in cells that lack de novo nucleoside synthesis pathways, and are also necessary for the uptake of cytotoxic nucleosides used for cancer and viral chemotherapies. Multiple alternatively spliced variants, encoding the same protein, have been found for this gene.

Source: NCBI Gene 2030 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 70 total — 1 pathogenic
• Druggable target: yes — 65 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_001372327

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11003
Approved symbol	SLC29A1
Name	solute carrier family 29 member 1 (Augustine blood group)
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000112759
Ensembl biotype	protein_coding
OMIM	602193
Entrez	2030

Gene structure

Transcript identifiers

Ensembl transcripts: 117 — 111 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000371708, ENST00000371713, ENST00000371724, ENST00000371731, ENST00000371740, ENST00000371755, ENST00000393841, ENST00000393844, ENST00000472176, ENST00000642613, ENST00000642777, ENST00000643028, ENST00000643152, ENST00000643869, ENST00000645259, ENST00000645607, ENST00000645692, ENST00000646251, ENST00000646582, ENST00000646878, ENST00000647460, ENST00000651428, ENST00000652453, ENST00000652680, ENST00000892020, ENST00000892021, ENST00000892022, ENST00000892023, ENST00000892024, ENST00000892025, ENST00000892026, ENST00000892027, ENST00000892028, ENST00000892029, ENST00000892030, ENST00000892031, ENST00000892032, ENST00000892033, ENST00000892034, ENST00000892035, ENST00000892036, ENST00000892037, ENST00000892038, ENST00000892039, ENST00000892040, ENST00000892041, ENST00000892042, ENST00000892043, ENST00000892044, ENST00000892045, ENST00000892046, ENST00000892047, ENST00000892048, ENST00000892049, ENST00000892050, ENST00000892051, ENST00000892052, ENST00000892053, ENST00000892054, ENST00000892055, ENST00000892056, ENST00000892057, ENST00000892058, ENST00000892059, ENST00000892060, ENST00000916875, ENST00000916876, ENST00000916877, ENST00000916878, ENST00000916879, ENST00000916880, ENST00000916881, ENST00000916882, ENST00000916883, ENST00000916884, ENST00000916885, ENST00000916886, ENST00000916887, ENST00000916888, ENST00000916889, ENST00000916890, ENST00000916891, ENST00000916892, ENST00000916893, ENST00000916894, ENST00000967779, ENST00000967780, ENST00000967781, ENST00000967782, ENST00000967783, ENST00000967784, ENST00000967785, ENST00000967786, ENST00000967787, ENST00000967788, ENST00000967789, ENST00000967790, ENST00000967791, ENST00000967792, ENST00000967793, ENST00000967794, ENST00000967795, ENST00000967796, ENST00000967797, ENST00000967798, ENST00000967799, ENST00000967800, ENST00000967801, ENST00000967802, ENST00000967803, ENST00000967804, ENST00000967805, ENST00000967806, ENST00000967807, ENST00000967808, ENST00000967809, ENST00000967810

RefSeq mRNA: 6 — MANE Select: NM_001372327 NM_001078175, NM_001078177, NM_001304462, NM_001304465, NM_001304466, NM_001372327

CCDS: CCDS4908

Canonical transcript exons

ENST00000371755 — 13 exons

Exon	Start	End
ENSE00001140395	44232807	44233006
ENSE00001140400	44232343	44232428
ENSE00001140427	44230347	44230481
ENSE00001140433	44229907	44230046
ENSE00001140451	44229390	44229471
ENSE00003472452	44227263	44227342
ENSE00003565986	44229589	44229791
ENSE00003572885	44231364	44231461
ENSE00003604848	44230568	44230665
ENSE00003658113	44230811	44230889
ENSE00003687885	44231998	44232106
ENSE00003820506	44233417	44234142
ENSE00003830106	44223595	44223641

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 99.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.7029 / max 1222.0246, expressed in 1811 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67986	27.2978	1665
67984	17.3547	1573
67982	3.5146	1113
67983	2.4161	919
67987	1.5402	819
67995	0.3957	141
67981	0.2636	105
67994	0.1962	108
67985	0.1563	56
67991	0.1275	40

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	99.15	gold quality
right coronary artery	UBERON:0001625	98.74	gold quality
apex of heart	UBERON:0002098	98.28	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.25	gold quality
right adrenal gland cortex	UBERON:0035827	98.04	gold quality
right adrenal gland	UBERON:0001233	98.01	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.01	gold quality
lower esophagus	UBERON:0013473	97.95	gold quality
ascending aorta	UBERON:0001496	97.87	gold quality
thoracic aorta	UBERON:0001515	97.85	gold quality
body of stomach	UBERON:0001161	97.82	gold quality
right atrium auricular region	UBERON:0006631	97.81	gold quality
left adrenal gland cortex	UBERON:0035825	97.74	gold quality
left adrenal gland	UBERON:0001234	97.72	gold quality
aorta	UBERON:0000947	97.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.38	gold quality
descending thoracic aorta	UBERON:0002345	97.35	gold quality
popliteal artery	UBERON:0002250	97.34	gold quality
tibial artery	UBERON:0007610	97.34	gold quality
cardiac atrium	UBERON:0002081	97.27	gold quality
left coronary artery	UBERON:0001626	97.21	gold quality
omental fat pad	UBERON:0010414	97.08	gold quality
peritoneum	UBERON:0002358	97.03	gold quality
adrenal cortex	UBERON:0001235	97.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.99	gold quality
coronary artery	UBERON:0001621	96.92	gold quality
tendon of biceps brachii	UBERON:0008188	96.87	gold quality
body of pancreas	UBERON:0001150	96.80	gold quality
skin of leg	UBERON:0001511	96.65	gold quality
adrenal gland	UBERON:0002369	96.61	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-109979	yes	512.19
E-MTAB-7008	yes	241.59
E-MTAB-9388	yes	8.46
E-ANND-3	yes	7.74
E-CURD-112	yes	4.15
E-ENAD-17	no	220.40
E-MTAB-9801	no	3.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, DDIT3, HIF1A, JUN, MAZ, SP1, TP53

miRNA regulators (miRDB)

36 targeting SLC29A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-6877-3P	98.98	65.83	560

Literature-anchored findings (GeneRIF, showing 40)

• When ENT1 is expressed in yeast, glycine residue 179 is critical not only to the ability of ENT1 to transport uridine but also as a determinant of ENT1 sensitivity to inhibition by nitrobenzylthioinosine. (PMID:11814344)
• role in functional and molecular characterization of nucleobase transport (PMID:12006583)
• Expression of 5NT and reduced hENT1 in leukemic blasts at diagnosis are correlated with clinical outcome and may play a role in resistance mechanisms to ara-C in patients with AML. (PMID:12008078)
• hCNT1 and hENT1 are expressed in polarized MDCK cells on the apical and basolateral membrane, respectively, allowing vectorial transport in both directions depending on the relative activity of each transporter for their substrates (PMID:12097333)
• an immunohistochemical method to assess the ENT1 abundance of cells in tumor tissue was used to study ENT1 differential expression in Reed-Sternberg cells of Hodgkin’s disease (PMID:12389626)
• hENT1 and hENT2 on the basolateral membrane function with concentrative nucleoside transporters on the apical membrane to mediate active reabsorption of nucleosides within the kidney. (PMID:12527552)
• Equilibrative nucleoside transporters (hENT1, hENT2) together with adenosine kinase and 5’-nucleotidase play a crucial role in the regulation of CFTR through an adenosine-dependent pathway in human airway epithelia. (PMID:12820662)
• ENT1 is expressed on the mitochondrial membrane and enhances the mitochondrial toxicity of nucleoside drugs such as FIAU (PMID:14607828)
• An amino acid residue (Leu92) of hENT1, when mutated, selectively alters the affinity of hENT1 to transport the nucleosides inosine and guanosine and its sensitivity to the inhibitors NBMPR and dilazep. (PMID:14759222)
• hENT1 was most frequently found in benign and malignant follicular center cells. (PMID:15529184)
• Transmembrane domains of human ENT1 interact and are important in conferring sensitivity to NBMPR. (PMID:15557207)
• The down-regulation of the ENT1 gene is expected to result in nucleotide deficiency in addition to blockage of Ara-C influx. (PMID:15632314)
• the corresponding residues in TMs 1 and 11 of hENT1, hENT2, and CeENT1 are important for dipyridamole interactions and nucleoside transport. (PMID:15649894)
• hypoxia-increased extracellular adenosine may result from reduced hENT1-adenosine transport in HUVEC. (PMID:15933265)
• decreased expression of human equilibrative nucleoside transporter, which transports ara-C across the cell membrane, appears to be a major factor in ara-C resistance in childhood AML (PMID:16333246)
• analysis of interspecies differences in the mitochondrial targeting signal of the equilibrative nucleoside transporter 1 (PMID:16595656)
• Functional single nucleotide polymorphism haplotypes were identified in ENT1. (PMID:16609362)
• Nitric oxide reduces SLC29A1 promoter activity in fetal endothelium from gestational diabetes. (PMID:16688763)
• role of ENT1 in nucleoside-derived drug bioavailability and action in mantle cell lymphoma (PMID:16818266)
• role of ENT1 in nucleoside-derived drug bioavailability and action in mantle cell lymphoma (PMID:16818276)
• Findings provide fundamental and useful information for genotyping SLC29a1 in Japanese and probably other Asian populations. (PMID:16858130)
• Putative consensus sites for transcription factors exist within the hENT1 promoter. (PMID:17162590)
• transcripts for ENT1 protein in human kidneys and in cultured proximal tubule cells suggest involvement of ENT1 in renal handling of nucleosides and nucleoside drugs (PMID:17409283)
• The absence of human equilibrative nucleoside transporter 1 expression predicts nonresponse to gemcitabine-containing chemotherapy in non-small cell lung cancer (PMID:17658213)
• Human cardiac microvascular endothelial cells rely on ENT1 for nucleoside transport with little contribution from ENT2. (PMID:17921321)
• These data suggest that selected genes of the SLC28 and SLC29 families are not only targets of HIV-1 infection, but might also contribute to the development of adipose tissue alterations leading to lipodystrophy. (PMID:17926640)
• Reduced hENT1-mediated adenosine transport in high D-glucose may result from increased Sp1 binding to SLC29A1 promoter down-regulating hENT1 expression. (PMID:18064606)
• On univariate analysis, overexpression of hENT1 was associated with shorter overall survival. (PMID:18187485)
• Data suggest that in ENT1, Trp29 is positioned close to Met33, implicated in nucleoside and inhibitor recognition, and that Trp29 forms part of, or lies close to, the binding sites for dipyridamole, dilazep, NBMPR, soluflazine and draflazine. (PMID:18462193)
• In NSCLC and normal tissues expression of hENT1 and hCNT1 ranged from completely negative to high. (PMID:18600541)
• Report expression and hepatobiliary transport characteristics of ENT1 in sandwich-cultured human hepatocytes. (PMID:18635603)
• hPMEC from pre-eclampsia exhibit increased total transport (hENT1+hENT2), and maximal velocity (Vmax) for hENT2- (2-fold), but reduced Vmax for hENT1-mediated adenosine transport (PMID:18703227)
• These results define G24 as critical amino acid for ENT1 nucleoside uptake and suggest that mutations in TM1 may provide a mechanism for Ara-C resistance in CCRF-CEM Ara-C/8C cells. (PMID:19116148)
• Our modeling of ribavirin in erythrocytes on long-term administration of ribavirin suggests that the accumulation of ribavirin inside the cells is dependent on ENT1/Ent1 transport (PMID:19164463)
• down-regulated by activation of TbetaRII by TGF-beta1 in endothelium from umbilical veins (PMID:19193655)
• Human ENT1 transgenic mice exhibit increased expression and function of ENT1 in brain, accompanied by an increased behavioral response to ethanol and a decreased response to caffeine. (PMID:19222701)
• This evidence suggested that apical CNT3 and basolateral ENT2 are involved in proximal tubular reabsorption of adenosine and some nucleoside drugs and that apical ENT1 is involved in proximal tubular secretion of 2’-deoxyadenosine. (PMID:19297449)
• Pancreatic adenocarcinoma patients with a high expression of hENT1 and hCNT3 immunostaining have a significantly longer survival after adjuvant gemcitabine-based chemoradiation (PMID:19318496)
• Expression of hENT1 was significantly lower in beta-thalassemic cells (PMID:19349719)
• In vitro ara-CTP production by phoshorylation of cytarabine and mRNA levels of hENT1 were compared in HL60 cells (PMID:19428333)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc29a1b	ENSDARG00000054447
danio_rerio	slc29a1a	ENSDARG00000101289
mus_musculus	Slc29a1	ENSMUSG00000023942
rattus_norvegicus	Slc29a1	ENSRNOG00000019752
drosophila_melanogaster	Ent1	FBGN0031250

Paralogs (3): SLC29A4 (ENSG00000164638), SLC29A2 (ENSG00000174669), SLC29A3 (ENSG00000198246)

Protein

Protein identifiers

Equilibrative nucleoside transporter 1 — Q99808 (reviewed: Q99808)

Alternative names: Equilibrative nitrobenzylmercaptopurine riboside-sensitive nucleoside transporter, Nucleoside transporter, es-type, Solute carrier family 29 member 1

All UniProt accessions (11): A0A2R8Y567, A0A2R8Y6D1, A0A2R8Y801, A0A2R8Y854, A0A2R8YEH8, A0A2R8YFB9, A0A2R8YFI6, A0A2U3TZJ7, A0A2U3TZM5, A0A2U3TZM6, Q99808

UniProt curated annotations — full annotation on UniProt →

Function. Uniporter involved in the facilitative transport of nucleosides and nucleobases, and contributes to maintaining their cellular homeostasis. Functions as a Na(+)-independent transporter. Involved in the transport of nucleosides such as adenosine, guanosine, inosine, uridine, thymidine and cytidine. Also transports purine nucleobases (hypoxanthine, adenine, guanine) and pyrimidine nucleobases (thymine, uracil). Mediates basolateral nucleoside uptake into Sertoli cells, thereby regulating the transport of nucleosides in testis across the blood-testis barrier. Regulates inosine levels in brown adipocytes tissues (BAT) and extracellular inosine levels, which controls BAT-dependent energy expenditure.

Subunit / interactions. Identified in a complex with STOM.

Subcellular location. Basolateral cell membrane. Apical cell membrane. Cell membrane.

Tissue specificity. Expressed in testis at the blood-testis barrier (at protein level). Detected in erythrocytes (at protein level). Expressed at relatively high levels in cerebral cortex, particularly the frontal and parietal lobes, and the thalamus and basal ganglia (at protein level). In the midbrain expressed at moderate levels, whereas in the other areas of the brainstem, namely medulla and pons, cerebellum and the hippocampus expressed at lower amounts when compared to the other brain regions (at protein level). Expressed in Langerhans cells and lymphocytes in the pancreas (at protein level). Expressed in kidney, in polarized renal epithelial cells. Expressed in adipose tissues. Expressed in placenta. Expressed in small intestine.

Post-translational modifications. Glycosylated.

Activity regulation. Transporter activity is sensitive to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR). Inhibited by dilazep. Inhibited by dipyridamole. Inhibited by hypoxanthine. Inhibited by azidothymidine (AZT). Inhibited by dideoxycytidine (ddC). Inhibited by dideoxyinosine (ddI). Inhibited by draflazine. Inhibited by soluflazine. Inhibited by cladribine. Inhibited by capecitabine. Inhibited by clofarabine. Inhibited by ribavirin. Modestly inhibited by acyclovir. Modestly inhibited by 5-fluorouracil.

Domain organisation. Cys-414 near TM10 is a major determinant of nucleobase transport activity.

Miscellaneous. The absence of the protein in tumor cells is associated with reduced survival in patients with gemcitabine-treated pancreas adenocarcinoma.

Similarity. Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99808-1	1	yes
Q99808-2	2

RefSeq proteins (6): NP_001071643, NP_001071645, NP_001291391, NP_001291394, NP_001291395, NP_001359256* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002259	Eqnu_transpt	Family
IPR034764	ENT1/ENT2	Family
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF01733

Catalyzed reactions (Rhea), 11 shown:

• uracil(in) = uracil(out) (RHEA:69404)
• hypoxanthine(out) = hypoxanthine(in) (RHEA:71515)
• uridine(out) = uridine(in) (RHEA:71519)
• adenine(out) = adenine(in) (RHEA:71523)
• thymine(out) = thymine(in) (RHEA:71527)
• guanine(out) = guanine(in) (RHEA:71531)
• adenosine(in) = adenosine(out) (RHEA:75343)
• thymidine(in) = thymidine(out) (RHEA:75363)
• cytidine(in) = cytidine(out) (RHEA:75367)
• guanosine(in) = guanosine(out) (RHEA:75371)
• inosine(in) = inosine(out) (RHEA:75375)

UniProt features (96 total): mutagenesis site 31, helix 22, topological domain 12, transmembrane region 11, sequence variant 4, site 3, modified residue 3, turn 2, strand 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6OB7	X-RAY DIFFRACTION	2.3
8TZI	X-RAY DIFFRACTION	2.7
6OB6	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99808-F1	87.85	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 277 (not glycosylated); 288 (not glycosylated); 414 (essential for nucleobase transport)

Post-translational modifications (3): 254, 269, 273

Glycosylation sites (1): 48

Mutagenesis-validated functional residues (31):

Position	Phenotype
33	no effect on the transport activity for adenosine.
48	glycosylation-defective.
87	loss of nucleobase transport; when associated with s-193; s-213; s-222; s-297; s-333; s-378; s-414; s-416 and s-439. no
92	resistance to nitrobenzylmercaptopurine riboside (nbmpr) and dilazep but not dipyridamole.
92	increase in the transport capacity and decrease in affinity for inosine. increase in the transport capacity but no chang
154	decreased affinity for cytidine and adenosine but not uridine. resistance to azidothymidine (azt), dideoxyinosine (ddi),
179	reduction of the transport activity for adenosine.
193	loss of nucleobase transport; when associated with s-87; s-213; s-222; s-297; s-333; s-378; s-414; s-416 and s-439. no c
209	reduction of the transport activity for adenosine.
213	loss of nucleobase transport; when associated with s-87; s-193; s-222; s-297; s-333; s-378; s-414; s-416 and s-439. no c
222	loss of nucleobase transport; when associated with s-87; s-193; s-213; s-297; s-333; s-378; s-414; s-416 and s-439. no c
277	no effect on glycosylation.
288	no effect on glycosylation.
297	loss of nucleobase transport; when associated with s-87; s-193; s-213; s-222; s-333; s-378; s-414; s-416 and s-439. no c
308	reduction of the transport activity for adenosine.
333	loss of nucleobase transport; when associated with s-87; s-193; s-213; s-222; s-297; s-378; s-414; s-416 and s-439. no c
334	decrease in the transport capacity but no change in affinity for adenosine. resistance to dipyridamole and dilazep, litt
334	increase in the transport capacity but no change in affinity for adenosine. resistance to dipyridamole and increase in t
338	no change in the transport capacity but decrease in affinity for adenosine. resistance to dipyridamole, dilazep, nitrobe
338	impaired protein folding and/or altered trafficking. decrease in the transport capacity but no change in affinity for ad
338	decrease in the transport capacity for adenosine but no change in substrate affinity. resistance to dipyridamole, dilaze
338	impaired protein folding and/or altered trafficking. decrease in the transport capacity for adenosine but no change in s
338	decrease in the transport capacity and substrate affinity for adenosine. resistance to dipyridamole, dilazep, nitrobenzy
378	loss of nucleobase transport; when associated with s-87; s-193; s-213; s-222; s-297; s-333; s-414; s-416 and s-439. no c
390	no effect on the transport activity for adenosine.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-83936	Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane
R-HSA-9748787	Azathioprine ADME
R-HSA-9755088	Ribavirin ADME
R-HSA-382551	Transport of small molecules
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-9748784	Drug ADME

MSigDB gene sets: 294 (showing top): CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEUROTRANSMITTER_UPTAKE, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_XENOBIOTIC_TRANSMEMBRANE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_DN, GOBP_CELL_CELL_SIGNALING, PATIL_LIVER_CANCER, GTGCCTT_MIR506, MAHAJAN_RESPONSE_TO_IL1A_DN, UEDA_PERIFERAL_CLOCK

GO Biological Process (29): neurotransmitter uptake (GO:0001504), nucleobase-containing compound metabolic process (GO:0006139), AMP catabolic process (GO:0006196), xenobiotic metabolic process (GO:0006805), neurotransmitter transport (GO:0006836), xenobiotic transmembrane transport (GO:0006855), lactation (GO:0007595), nucleobase transport (GO:0015851), adenine transport (GO:0015853), nucleoside transport (GO:0015858), purine nucleoside transmembrane transport (GO:0015860), cytidine transport (GO:0015861), uridine transmembrane transport (GO:0015862), adenosine transport (GO:0032238), inosine transport (GO:0035340), hypoxanthine transport (GO:0035344), thymine transport (GO:0035364), ADP catabolic process (GO:0046032), response to antibiotic (GO:0046677), excitatory postsynaptic potential (GO:0060079), cellular response to glucose stimulus (GO:0071333), cellular response to hypoxia (GO:0071456), pyrimidine-containing compound transmembrane transport (GO:0072531), transport across blood-brain barrier (GO:0150104), nucleoside transmembrane transport (GO:1901642), guanine transmembrane transport (GO:1903716), uracil transmembrane transport (GO:1903791), pyrimidine nucleobase transmembrane transport (GO:1904082), purine nucleobase transmembrane transport (GO:1904823)

GO Molecular Function (10): neurotransmitter transmembrane transporter activity (GO:0005326), nucleoside transmembrane transporter activity (GO:0005337), adenine transmembrane transporter activity (GO:0015207), guanine transmembrane transporter activity (GO:0015208), uracil transmembrane transporter activity (GO:0015210), purine nucleoside transmembrane transporter activity (GO:0015211), cytidine transmembrane transporter activity (GO:0015212), uridine transmembrane transporter activity (GO:0015213), pyrimidine- and adenosine-specific:sodium symporter activity (GO:0015389), transmembrane transporter activity (GO:0022857)

GO Cellular Component (6): plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), presynapse (GO:0098793), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Drug ADME	2
Transport of vitamins, nucleosides, and related molecules	1
SLC-mediated transmembrane transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleoside transmembrane transport	3
purine nucleobase transmembrane transporter activity	3
cellular anatomical structure	3
neurotransmitter transport	2
purine ribonucleotide catabolic process	2
transmembrane transport	2
purine nucleobase transport	2
pyrimidine nucleoside transport	2
nucleoside transport	2
pyrimidine nucleobase transmembrane transporter activity	2
pyrimidine nucleoside transmembrane transporter activity	2
plasma membrane region	2
synapse	2
import into cell	1
primary metabolic process	1
purine ribonucleoside monophosphate catabolic process	1
AMP metabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
transport	1
xenobiotic transport	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
nitrogen compound transport	1
nucleobase-containing compound transport	1
carbohydrate derivative transport	1
purine-containing compound transmembrane transport	1
pyrimidine-containing compound transmembrane transport	1
pyrimidine nucleobase transport	1
purine ribonucleoside diphosphate catabolic process	1
ADP metabolic process	1
response to chemical	1
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	1
transmembrane transporter activity	1
nucleobase-containing compound transmembrane transporter activity	1
carbohydrate derivative transmembrane transporter activity	1
adenine transport	1
guanine transmembrane transport	1

Protein interactions and networks

STRING

1316 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC29A1	SLC28A1	O00337	894
SLC29A1	SLC28A3	Q9HAS3	892
SLC29A1	SLC28A2	O43868	883
SLC29A1	ADORA1	P30542	880
SLC29A1	DCK	P27707	875
SLC29A1	ADA	P00813	734
SLC29A1	ADK	P55263	733
SLC29A1	ADORA2A	P29274	715
SLC29A1	CDA	P32320	708
SLC29A1	RRM1	P23921	697
SLC29A1	CALM1	P02593	685
SLC29A1	CALML6	Q8TD86	644
SLC29A1	CALML3	P27482	644
SLC29A1	CALML5	Q9NZT1	644
SLC29A1	CALML4	Q96GE6	644

IntAct

104 interactions, top by confidence:

A	B	Type	Score
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3B1	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
SLC22A16	APBA3	psi-mi:“MI:0914”(association)	0.530
TM2D2	TMEM97	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
SIDT2	AP3D1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3D1	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
SLC29A1	SRC	psi-mi:“MI:0915”(physical association)	0.400
SLC29A1	HTR2C	psi-mi:“MI:0915”(physical association)	0.370
SLC29A1	CREB3	psi-mi:“MI:0915”(physical association)	0.370
AQP1	FLOT1	psi-mi:“MI:0914”(association)	0.350
ATP2B4	FLOT1	psi-mi:“MI:0914”(association)	0.350
UPK1A	TMEM223	psi-mi:“MI:0914”(association)	0.350
ADGRE5	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
SIGLECL1	KIAA1324L	psi-mi:“MI:0914”(association)	0.350
SLC18A1	LIMK2	psi-mi:“MI:0914”(association)	0.350
FPR2	GPR89A	psi-mi:“MI:0914”(association)	0.350

BioGRID (172): SLC29A1 (Affinity Capture-MS), SLC29A1 (Two-hybrid), SLC29A1 (Proximity Label-MS), SLC29A1 (Two-hybrid), SLC29A1 (Proximity Label-MS), SRC (Affinity Capture-MS), SLC29A1 (Affinity Capture-MS), SLC29A1 (Affinity Capture-MS), SLC29A1 (Affinity Capture-MS), SLC29A1 (Affinity Capture-MS), SLC29A1 (Affinity Capture-MS), SLC29A1 (Affinity Capture-MS), SLC29A1 (Affinity Capture-MS), SLC29A1 (Affinity Capture-MS), SLC29A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4ILB2, A0A8M9Q308, A1A4N1, A2CER7, A5D7V7, A8WGF7, B0S5Y3, B2RXV4, B5X4H8, O00400, O00476, O01735, O23596, P30638, P36836, P46029, P60815, Q11073, Q16348, Q28722, Q28FF3, Q503P5, Q5F4B8, Q5RBM3, Q5XGK0, Q63424, Q6AYY8, Q6DDL7, Q6DIT7, Q6GMG6, Q6PB15, Q7Z3Q1, Q84XI3, Q86WB7, Q91X85, Q944P0, Q99808, Q99J27, Q9BZD2, Q9C8X2

Diamond homologs: A1A4N1, O54698, O54699, Q14542, Q61672, Q80WK7, Q99808, Q99P65, Q9BZD2, Q9JIM1, Q9NBV4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKCD	“up-regulates activity”	SLC29A1	phosphorylation
CSNK2A1	“up-regulates activity”	SLC29A1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
VEGFR2 mediated cell proliferation	5	33.2×	6e-05
Signaling by SCF-KIT	5	14.4×	1e-03
Regulation of RAS by GAPs	5	11.2×	2e-03
Signaling by BRAF and RAF1 fusions	5	9.9×	3e-03
Class A/1 (Rhodopsin-like receptors)	7	6.0×	3e-03
GPCR ligand binding	8	6.0×	2e-03
G alpha (i) signalling events	10	4.5×	2e-03
Signaling by GPCR	9	4.2×	3e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

70 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	41
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
429191	NM_001372327.1(SLC29A1):c.1159A>C (p.Thr387Pro)	Pathogenic

SpliceAI

2684 predictions. Top by Δscore:

Variant	Effect	Δscore
6:44229467:CTCAG:C	donor_loss	1.0000
6:44229468:TCAG:T	donor_loss	1.0000
6:44229469:CAGG:C	donor_loss	1.0000
6:44229470:AGGT:A	donor_loss	1.0000
6:44229471:GG:G	donor_loss	1.0000
6:44229472:G:GC	donor_loss	1.0000
6:44229473:T:A	donor_loss	1.0000
6:44229578:A:AG	acceptor_gain	1.0000
6:44229579:A:G	acceptor_gain	1.0000
6:44229584:T:TA	acceptor_gain	1.0000
6:44229584:TGCA:T	acceptor_loss	1.0000
6:44229585:GCAGT:G	acceptor_loss	1.0000
6:44229586:CAGTA:C	acceptor_loss	1.0000
6:44229587:A:AG	acceptor_gain	1.0000
6:44229587:A:T	acceptor_loss	1.0000
6:44229588:G:GA	acceptor_gain	1.0000
6:44229588:GT:G	acceptor_gain	1.0000
6:44229588:GTA:G	acceptor_gain	1.0000
6:44229588:GTAT:G	acceptor_gain	1.0000
6:44229588:GTATT:G	acceptor_gain	1.0000
6:44229787:CAGAG:C	donor_gain	1.0000
6:44229788:AGAG:A	donor_gain	1.0000
6:44229788:AGAGG:A	donor_loss	1.0000
6:44229789:GAG:G	donor_gain	1.0000
6:44229789:GAGG:G	donor_gain	1.0000
6:44229790:AG:A	donor_gain	1.0000
6:44229791:GG:G	donor_gain	1.0000
6:44229792:G:GG	donor_gain	1.0000
6:44229792:GTGA:G	donor_loss	1.0000
6:44229891:T:TA	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000428509 (6:44231005 G>A), RS1000488400 (6:44218369 G>A), RS1000490285 (6:44219638 A>G), RS1000851430 (6:44217742 C>A), RS1000892546 (6:44223786 G>A,C,T), RS1000941425 (6:44223612 C>G,T), RS1001048482 (6:44224251 A>C), RS1001050046 (6:44229637 G>A), RS1001220928 (6:44218945 C>A), RS1001273159 (6:44218693 C>T), RS1001331226 (6:44223210 G>C), RS1001394577 (6:44224608 C>A), RS1001438264 (6:44228953 A>C), RS1002378071 (6:44224389 G>A), RS1002629640 (6:44217846 A>G)

Disease associations

OMIM: gene MIM:602193 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): fetal erythroblastosis (MONDO:0006760)

Orphanet (1): Hemolytic disease due to fetomaternal alloimmunization (Orphanet:275938)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004602_113	Mean corpuscular volume	6.000000e-11
GCST005956_58	Waist-to-hip ratio adjusted for BMI	7.000000e-26
GCST005957_1	Waist-to-hip ratio adjusted for BMI (age <50)	2.000000e-14
GCST005958_2	Waist-to-hip ratio adjusted for BMI (age >50)	2.000000e-19
GCST005962_2	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-31
GCST006979_282	Heel bone mineral density	3.000000e-11
GCST90002390_438	Mean corpuscular hemoglobin	2.000000e-24
GCST90002396_298	Mean reticulocyte volume	4.000000e-10
GCST90002397_146	Mean spheric corpuscular volume	3.000000e-31
GCST90002404_261	Red cell distribution width	2.000000e-12

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009270	heel bone mineral density
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004899	Erythroblastosis, Fetal	C12.050.703.277.060; C15.378.295; C16.300.060; C16.614.304; C20.306

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1997 (SINGLE PROTEIN), CHEMBL6066081 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

65 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 584,343 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL111	RIMONABANT	4	15,726
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1201203	BENZTROPINE	4	9,334
CHEMBL1201303	PYRVINIUM	4	1,797
CHEMBL1201304	INDOCYANINE GREEN ACID FORM	4	7,044
CHEMBL1201346	BALSALAZIDE	4	8,319
CHEMBL1255800	FIDAXOMICIN	4	2,010
CHEMBL1303	ROTIGOTINE	4	832
CHEMBL1401	NITAZOXANIDE	4	9,504
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL142635	NAFTOPIDIL	4	3,611
CHEMBL1428	NIMODIPINE	4	32,587
CHEMBL146095	GLAFENINE	4	2,714
CHEMBL1480	FELODIPINE	4	30,761
CHEMBL1495	OXYPHENCYCLIMINE	4	1,670
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL1617	RIFAXIMIN	4	13,380
CHEMBL178	DAUNORUBICIN	4	203,756
CHEMBL180022	NERATINIB	4	9,404
CHEMBL190461	CANNABIDIOL	4	26,379
CHEMBL219916	DOMPERIDONE	4
CHEMBL231779	APIXABAN	4
CHEMBL252556	IDEBENONE	4
CHEMBL255863	NILOTINIB	4
CHEMBL269732	TACROLIMUS ANHYDROUS	4
CHEMBL288441	BOSUTINIB	4
CHEMBL3301612	ENCORAFENIB	4
CHEMBL3545185	SELINEXOR	4
CHEMBL374478	RIFAMPIN	4
CHEMBL376140	TIGECYCLINE	4

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
SLC29A1 Overexpression	Gemcitabine	Pancreatic Adenocarcinoma	Sensitivity/Response	CIViC B	EID10145

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs747199	Efficacy	3	gemcitabine;paclitaxel	Breast Neoplasms
rs760370	Efficacy	3	gemcitabine	Neoplasms
rs760370	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection
rs760370	Efficacy	3	tipiracil hydrochloride;trifluridine	Colorectal Neoplasms
rs9394992	Toxicity	3	gemcitabine	Pancreatic Neoplasms
rs9394992	Efficacy	3	tipiracil hydrochloride;trifluridine	Colorectal Neoplasms

PharmGKB variants

10 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs70914	SLC29A1		0.00	0
rs324148	SLC29A1		0.00	0
rs731780	SLC29A1		0.00	0
rs747199	SLC29A1	3	0.00	1	gemcitabine;paclitaxel
rs760370	SLC29A1	3	3.25	3	gemcitabine;peginterferon alfa-2a;peginterferon alfa-2b;ribavirin;tipiracil hydrochloride;trifluridine
rs3778504	SLC29A1		0.00	0
rs9394992	SLC29A1	3	3.25	2	gemcitabine;tipiracil hydrochloride;trifluridine
rs3734703	SLC29A1		0.00	0
rs3734704	SLC29A1	3	0.00	1	bevacizumab
rs693955	POLR1C, SLC29A1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC29 family

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
nitrobenzylmercaptopurine ribonucleoside	Inhibition	9.7	pKi
draflazine	Inhibition	9.6	pKi
KF24345	Inhibition	9.4	pKi
[3H]nitrobenzylmercaptopurine ribonucleoside		9.3	pKd
NBTGR	Inhibition	9.3	pKi
EOS-984	Inhibition	9.0	pIC50
dilazep	Inhibition	9.0	pKi
dipyridamole	Inhibition	8.8	pKi
ticagrelor	Inhibition	7.3	pKi

Binding affinities (BindingDB)

33 measured of 80 human assays (80 total across all organisms); most potent 33 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
NBTI	KI	0.43 nM
2-{4,8-bis(azocan-1-yl)-6-[bis(2-hydroxyethyl)amino]pyrimido[5,4-d][1,3]diazin-2-ylamino}ethan-1-ol	KI	0.49 nM
2-{4,8-bis(azonan-1-yl)-6-[bis(2-hydroxyethyl)amino]pyrimido[5,4-d][1,3]diazin-2-ylamino}ethan-1-ol	KI	0.77 nM
2-{4,8-bis(azepan-1-yl)-6-[bis(2-hydroxyethyl)amino]pyrimido[5,4-d][1,3]diazin-2-ylamino}ethan-1-ol	KI	0.86 nM
2-({6-[(2-hydroxyethyl)[2-(propan-2-yloxy)ethyl]amino]-4,8-bis(piperidin-1-yl)pyrimido[5,4-d][1,3]diazin-2-yl}[2-(propan-2-yloxy)ethyl]amino)ethan-1-ol	KI	4.3 nM
Dipyridamine	KI	8.18 nM
{2-[(6-{bis[2-(formyloxy)ethyl]amino}-4,8-bis(piperidin-1-yl)pyrimido[5,4-d][1,3]diazin-2-yl)[2-(formyloxy)ethyl]amino]ethyl} formate	KI	8.2 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis[(2,2-dimethylpropyl)amino]pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	14.7 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(cyclopentylamino)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	15.8 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(tert-butylamino)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	16.8 nM
2-[(6-{bis[2-(acetyloxy)ethyl]amino}-4,8-bis(piperidin-1-yl)pyrimido[5,4-d][1,3]diazin-2-yl)[2-(acetyloxy)ethyl]amino]ethyl acetate	KI	17.1 nM
2-{[4,8-bis(azocan-1-yl)-6-[(2-hydroxyethyl)amino]pyrimido[5,4-d][1,3]diazin-2-yl]amino}ethan-1-ol	KI	21.2 nM
2-{[4,8-bis(azonan-1-yl)-6-[(2-hydroxyethyl)amino]pyrimido[5,4-d][1,3]diazin-2-yl]amino}ethan-1-ol	KI	38 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis[(2-methylpropyl)amino]pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	38 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(cyclohexylamino)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	53.1 nM
2-N,2-N,6-N,6-N-tetrakis(2-methoxyethyl)-4,8-bis(piperidin-1-yl)pyrimido[5,4-d][1,3]diazine-2,6-diamine	KI	91.6 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(pyrrolidin-1-yl)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	99.7 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(cyclobutylamino)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	104 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis[(3-methylbutyl)amino]pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	121 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(butylamino)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	136 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(pentylamino)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	140 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(propan-2-ylamino)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	191 nM
2-{4,8-bis({8-azabicyclo[3.2.1]octan-8-yl})-6-[bis(2-hydroxyethyl)amino]pyrimido[5,4-d][1,3]diazin-2-ylamino}ethan-1-ol	KI	193 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(diethylamino)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	216 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(dimethylamino)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	217 nM
Clinium	KI	280 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(propylamino)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	300 nM
2-{[6-(2-hydroxyethoxy)-4,8-bis(piperidin-1-yl)pyrimido[5,4-d][1,3]diazin-2-yl]oxy}ethan-1-ol	KI	325 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(morpholin-4-yl)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	393 nM
2-({6-[bis(2-hydroxyethyl)amino]-4,8-bis(cyclopropylamino)pyrimido[5,4-d][1,3]diazin-2-yl}(2-hydroxyethyl)amino)ethan-1-ol	KI	428 nM
benzyl 4-{2,6-bis[bis(2-hydroxyethyl)amino]-8-(piperazin-1-yl)pyrimido[5,4-d][1,3]diazin-4-yl}piperazine-1-carboxylate	KI	449 nM
2-{[4,8-bis(butylamino)-6-[(2-hydroxyethyl)amino]pyrimido[5,4-d][1,3]diazin-2-yl]amino}ethan-1-ol	KI	489 nM
2-({6-[(2-hydroxyethyl)amino]-4,8-bis(piperidin-1-yl)pyrimido[5,4-d][1,3]diazin-2-yl}amino)ethan-1-ol	KI	691 nM

ChEMBL bioactivities

323 potent at pChembl≥5 of 400 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.74	Ki	0.018	nM	CHEMBL571939
10.19	Ki	0.064	nM	CHEMBL569223
10.00	IC50	0.1	nM	DILAZEP
9.59	Kd	0.26	nM	CHEMBL569224
9.55	Ki	0.28	nM	DRAFLAZINE
9.52	IC50	0.3	nM	NITROBENZYLMERCAPTOPURINE RIBONUCLEOSIDE
9.49	Kd	0.32	nM	CHEMBL569224
9.44	Kd	0.36	nM	CHEMBL569224
9.40	Kd	0.4	nM	CHEMBL569224
9.37	Ki	0.43	nM	NITROBENZYLMERCAPTOPURINE RIBONUCLEOSIDE
9.35	Ki	0.45	nM	CHEMBL260570
9.31	Ki	0.49	nM	CHEMBL243304
9.19	Ki	0.64	nM	CHEMBL610234
9.15	Ki	0.7	nM	NITROBENZYLMERCAPTOPURINE RIBONUCLEOSIDE
9.15	Ki	0.7079	nM	NITROBENZYLMERCAPTOPURINE RIBONUCLEOSIDE
9.11	Ki	0.77	nM	CHEMBL242657
9.07	Ki	0.86	nM	CHEMBL243096
9.04	Kd	0.91	nM	CHEMBL569224
9.03	Ki	0.94	nM	CHEMBL608795
9.03	Ki	0.94	nM	DRAFLAZINE
9.00	IC50	1	nM	NITROBENZYLMERCAPTOPURINE RIBONUCLEOSIDE
8.96	Ki	1.1	nM	CHEMBL394171
8.85	IC50	1.4	nM	CHEMBL571939
8.75	Ki	1.778	nM	CHEMBL61773
8.68	Ki	2.1	nM	CHEMBL239246
8.64	Ki	2.3	nM	CHEMBL610047
8.59	IC50	2.6	nM	NITROBENZYLMERCAPTOPURINE RIBONUCLEOSIDE
8.56	IC50	2.754	nM	CHEMBL260688
8.55	IC50	2.8	nM	CHEMBL3353069
8.52	Ki	3	nM	CHEMBL607955
8.49	IC50	3.2	nM	CHEMBL3353072
8.44	Ki	3.6	nM	CHEMBL610236
8.44	IC50	3.6	nM	NITROBENZYLMERCAPTOPURINE RIBONUCLEOSIDE
8.43	Ki	3.7	nM	CHEMBL610235
8.42	Ki	3.802	nM	CHEMBL512162
8.42	Kd	3.8	nM	CHEMBL569224
8.41	Ki	3.88	nM	CHEMBL512162
8.37	Ki	4.3	nM	CHEMBL242027
8.36	Ki	4.365	nM	CHEMBL61741
8.34	IC50	4.6	nM	CHEMBL3353074
8.34	Ki	4.571	nM	CHEMBL61915
8.32	IC50	4.786	nM	CHEMBL259866
8.29	IC50	5.1	nM	CHEMBL569223
8.28	Ki	5.3	nM	CHEMBL609378
8.28	IC50	5.3	nM	DRAFLAZINE
8.27	Ki	5.4	nM	CHEMBL608794
8.26	IC50	5.495	nM	CHEMBL260570
8.15	Ki	7.079	nM	CHEMBL432688
8.12	IC50	7.6	nM	NITROBENZYLMERCAPTOPURINE RIBONUCLEOSIDE
8.09	Ki	8.2	nM	CHEMBL442098

PubChem BioAssay actives

332 with measured affinity, of 1741 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[6-[2-[[(2S,3S,4R,5R)-3,4-dihydroxy-5-[6-[(4-nitrophenyl)methylamino]purin-9-yl]oxolan-2-yl]methylsulfanyl]ethylamino]-6-oxohexyl]-3-iodobenzamide	447182: Displacement of SAENTA-fluorescein from human ENT1 in HL60 cells by flow cytometry	ki	<0.0001	uM
3-[4-[3-(3,4,5-trimethoxybenzoyl)oxypropyl]-1,4-diazepan-1-yl]propyl 3,4,5-trimethoxybenzoate	1912447: Inhibition of the equilibrative nucleoside transporter (ENT1, SLC29A1) as assessed by GPCR-mediated changes in cell morphology using the impedance-based transporter activity through receptor activation (TRACT) assay (PubChem AID: 1745861)	ic50	0.0001	uM
N-[6-[2-[[(2S,3S,4R,5R)-3,4-dihydroxy-5-[6-[(4-nitrophenyl)methylamino]purin-9-yl]oxolan-2-yl]methylsulfanyl]ethylamino]-6-oxohexyl]-4-fluorobenzamide	447182: Displacement of SAENTA-fluorescein from human ENT1 in HL60 cells by flow cytometry	ki	0.0001	uM
N-[6-[2-[[(2S,3S,4R,5R)-3,4-dihydroxy-5-[6-[(4-nitrophenyl)methylamino]purin-9-yl]oxolan-2-yl]methylsulfanyl]ethylamino]-6-oxohexyl]-3,6-dihydroxy-3’-oxospiro[1,2-dihydroxanthene-9,1’-2-benzofuran]-5’-carboxamide	447184: Binding affinity to human ENT1 in HL60 cells by flow cytometry	kd	0.0003	uM
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-[(4-nitrophenyl)methylsulfanyl]purin-9-yl]oxolane-3,4-diol	255288: Percent inhibition against ADO transporter at 1 uM nonselective	ic50	0.0003	uM
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-(7-nitro-3,4-dihydro-1H-isoquinolin-2-yl)purin-9-yl]oxolane-3,4-diol	146819: Binding affinity of compound towards Nucleoside transporter es-type by facile competitive binding flow cytometric assay using the human K562 chronic melogenous leukemia cell line	ki	0.0004	uM
2-[[4,8-bis(azocan-1-yl)-2-[bis(2-hydroxyethyl)amino]pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol	1798344: Flow Cytometric Assay from Article 10.1021/jm070311l: “Synthesis, flow cytometric evaluation, and identification of highly potent dipyridamole analogues as equilibrative nucleoside transporter 1 inhibitors.”	ki	0.0005	uM
(3R,4S,5R)-2-[6-benzylsulfanyl-8-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	239557: Inhibition of [3H]NBTI binding to equilibrative nucleoside transport protein 1 (ENT1) in human erythrocyte membranes	ki	0.0006	uM
2-[[4,8-bis(azonan-1-yl)-2-[bis(2-hydroxyethyl)amino]pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol	1798344: Flow Cytometric Assay from Article 10.1021/jm070311l: “Synthesis, flow cytometric evaluation, and identification of highly potent dipyridamole analogues as equilibrative nucleoside transporter 1 inhibitors.”	ki	0.0008	uM
2-[[4,8-bis(azepan-1-yl)-2-[bis(2-hydroxyethyl)amino]pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol	1798344: Flow Cytometric Assay from Article 10.1021/jm070311l: “Synthesis, flow cytometric evaluation, and identification of highly potent dipyridamole analogues as equilibrative nucleoside transporter 1 inhibitors.”	ki	0.0009	uM
(3R,4S,5R)-2-[6-benzylsulfanyl-8-(cyclohexylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	239557: Inhibition of [3H]NBTI binding to equilibrative nucleoside transport protein 1 (ENT1) in human erythrocyte membranes	ki	0.0009	uM
(2R,3R,4S,5R)-2-[2-amino-6-[(4-nitrophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	309988: Displacement of SAENTA-fluorescein from human ENT1 in K562 cells after 45 mins by flow cytometry	ki	0.0011	uM
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-[(3-nitrophenyl)methylsulfanyl]purin-9-yl]oxolane-3,4-diol	392456: Inhibition of human ENT1	ki	0.0018	uM
(2R,3R,4S,5R)-2-[2-fluoro-6-[(4-nitrophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	309988: Displacement of SAENTA-fluorescein from human ENT1 in K562 cells after 45 mins by flow cytometry	ki	0.0021	uM
(3R,4S,5R)-2-[6-benzylsulfanyl-8-(pentylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	239557: Inhibition of [3H]NBTI binding to equilibrative nucleoside transport protein 1 (ENT1) in human erythrocyte membranes	ki	0.0023	uM
(2R,3R,4S,5R)-2-[2-amino-6-[(2-hydroxy-5-nitrophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	330912: Binding affinity to ENT1 transporter	ic50	0.0028	uM
2-[4-[2-(3,4,5-trimethoxybenzoyl)oxyethyl]piperazin-1-yl]ethyl 3,4,5-trimethoxybenzoate	1173514: Inhibition of human ENT1 expressed in porcine PK15NTD cells by cell-based [3H]5-uridine uptake assay	ic50	0.0028	uM
(3R,4S,5R)-2-[6-benzylsulfanyl-8-(cyclopropylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	239557: Inhibition of [3H]NBTI binding to equilibrative nucleoside transport protein 1 (ENT1) in human erythrocyte membranes	ki	0.0030	uM
4-[2,5-dimethyl-4-[4-(3,4,5-trimethoxybenzoyl)oxybutyl]piperazin-1-yl]butyl 3,4,5-trimethoxybenzoate	1173514: Inhibition of human ENT1 expressed in porcine PK15NTD cells by cell-based [3H]5-uridine uptake assay	ic50	0.0032	uM
(3R,4S,5R)-2-[6-benzylsulfanyl-8-(2-methylbutylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	239557: Inhibition of [3H]NBTI binding to equilibrative nucleoside transport protein 1 (ENT1) in human erythrocyte membranes	ki	0.0036	uM
(3R,4S,5R)-2-[6-benzylsulfanyl-8-(hexylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	239557: Inhibition of [3H]NBTI binding to equilibrative nucleoside transport protein 1 (ENT1) in human erythrocyte membranes	ki	0.0037	uM
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-[(4-iodophenyl)methylsulfanyl]purin-9-yl]oxolane-3,4-diol	392456: Inhibition of human ENT1	ki	0.0038	uM
2-[[2-[2-hydroxyethyl(2-propan-2-yloxyethyl)amino]-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidin-6-yl]-(2-propan-2-yloxyethyl)amino]ethanol	1798344: Flow Cytometric Assay from Article 10.1021/jm070311l: “Synthesis, flow cytometric evaluation, and identification of highly potent dipyridamole analogues as equilibrative nucleoside transporter 1 inhibitors.”	ki	0.0043	uM
(2R,3R,4S,5R)-2-[6-[(2,4-dichlorophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	392456: Inhibition of human ENT1	ki	0.0044	uM
4-[[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]sulfanylmethyl]benzonitrile	392456: Inhibition of human ENT1	ki	0.0046	uM
3-[4-[2-(3,4,5-trimethoxybenzoyl)oxyethyl]-1,4-diazepan-1-yl]propyl 3,4,5-trimethoxybenzoate	1173514: Inhibition of human ENT1 expressed in porcine PK15NTD cells by cell-based [3H]5-uridine uptake assay	ic50	0.0046	uM
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-[(3-nitrophenyl)sulfanylmethyl]purin-9-yl]oxolane-3,4-diol	330912: Binding affinity to ENT1 transporter	ic50	0.0048	uM
(3R,4S,5R)-2-[6-benzylsulfanyl-8-(propylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	239557: Inhibition of [3H]NBTI binding to equilibrative nucleoside transport protein 1 (ENT1) in human erythrocyte membranes	ki	0.0053	uM
1-[2-(4-amino-2,6-dichloroanilino)-2-oxoethyl]-4-[5,5-bis(4-fluorophenyl)pentyl]piperazine-2-carboxamide	1912447: Inhibition of the equilibrative nucleoside transporter (ENT1, SLC29A1) as assessed by GPCR-mediated changes in cell morphology using the impedance-based transporter activity through receptor activation (TRACT) assay (PubChem AID: 1745861)	ic50	0.0053	uM
(3R,4S,5R)-2-[6-benzylsulfanyl-8-(butylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	239557: Inhibition of [3H]NBTI binding to equilibrative nucleoside transport protein 1 (ENT1) in human erythrocyte membranes	ki	0.0054	uM
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-[[4-(trifluoromethoxy)phenyl]methylsulfanyl]purin-9-yl]oxolane-3,4-diol	392456: Inhibition of human ENT1	ki	0.0071	uM
Dipyridamole	1912447: Inhibition of the equilibrative nucleoside transporter (ENT1, SLC29A1) as assessed by GPCR-mediated changes in cell morphology using the impedance-based transporter activity through receptor activation (TRACT) assay (PubChem AID: 1745861)	ic50	0.0081	uM
2-[[2-[bis(2-formyloxyethyl)amino]-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidin-6-yl]-(2-formyloxyethyl)amino]ethyl formate	1798344: Flow Cytometric Assay from Article 10.1021/jm070311l: “Synthesis, flow cytometric evaluation, and identification of highly potent dipyridamole analogues as equilibrative nucleoside transporter 1 inhibitors.”	ki	0.0082	uM
(2R,3R,4S,5R)-2-[6-[(4-fluorophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	219062: Displacement of 5-(SAENTA)-X8-fluorescein from K562 cell nucleoside transporter	ki	0.0090	uM
(3R,4S,5R)-2-[6-benzylsulfanyl-8-(ethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	239557: Inhibition of [3H]NBTI binding to equilibrative nucleoside transport protein 1 (ENT1) in human erythrocyte membranes	ki	0.0095	uM
(2R,3R,4S,5R)-2-[6-[(4-bromophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	219062: Displacement of 5-(SAENTA)-X8-fluorescein from K562 cell nucleoside transporter	ki	0.0100	uM
(2R,3R,4S,5R)-2-[2-chloro-6-[(4-nitrophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	309988: Displacement of SAENTA-fluorescein from human ENT1 in K562 cells after 45 mins by flow cytometry	ki	0.0110	uM
(2R,3R,4S,5R)-2-[2-bromo-6-[(4-nitrophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	309988: Displacement of SAENTA-fluorescein from human ENT1 in K562 cells after 45 mins by flow cytometry	ki	0.0110	uM
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[2-iodo-6-[(4-nitrophenyl)methylsulfanyl]purin-9-yl]oxolane-3,4-diol	309988: Displacement of SAENTA-fluorescein from human ENT1 in K562 cells after 45 mins by flow cytometry	ki	0.0110	uM
(2R,3R,4S,5R)-2-[6-[(3-fluorophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	219062: Displacement of 5-(SAENTA)-X8-fluorescein from K562 cell nucleoside transporter	ki	0.0112	uM
(2R,3R,4S,5R)-2-[6-[(3,4-dichlorophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	392456: Inhibition of human ENT1	ki	0.0126	uM
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-[(3-iodophenyl)methylsulfanyl]purin-9-yl]oxolane-3,4-diol	219062: Displacement of 5-(SAENTA)-X8-fluorescein from K562 cell nucleoside transporter	ki	0.0138	uM
(2R,3R,4S,5R)-2-[6-[(4-chlorophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	219062: Displacement of 5-(SAENTA)-X8-fluorescein from K562 cell nucleoside transporter	ki	0.0142	uM
2-[[2-[bis(2-hydroxyethyl)amino]-4,8-bis(2-methylbutan-2-ylamino)pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol	296876: Inhibition of ENT1 in human K562 cells by flow cytometric assay	ki	0.0147	uM
2-[[2-[bis(2-hydroxyethyl)amino]-4,8-bis(2,2-dimethylpropylamino)pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol	1798344: Flow Cytometric Assay from Article 10.1021/jm070311l: “Synthesis, flow cytometric evaluation, and identification of highly potent dipyridamole analogues as equilibrative nucleoside transporter 1 inhibitors.”	ki	0.0147	uM
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-(6-nitro-3,4-dihydro-1H-isoquinolin-2-yl)purin-9-yl]oxolane-3,4-diol	146819: Binding affinity of compound towards Nucleoside transporter es-type by facile competitive binding flow cytometric assay using the human K562 chronic melogenous leukemia cell line	ki	0.0150	uM
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-[(4-methylphenyl)methylsulfanyl]purin-9-yl]oxolane-3,4-diol	392456: Inhibition of human ENT1	ki	0.0151	uM
2-[[2-[bis(2-hydroxyethyl)amino]-4,8-bis(cyclopentylamino)pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol	1798344: Flow Cytometric Assay from Article 10.1021/jm070311l: “Synthesis, flow cytometric evaluation, and identification of highly potent dipyridamole analogues as equilibrative nucleoside transporter 1 inhibitors.”	ki	0.0158	uM
(2R,3S,5R)-2-(hydroxymethyl)-5-[6-[(4-nitrophenyl)methylamino]purin-9-yl]oxolan-3-ol	330912: Binding affinity to ENT1 transporter	ic50	0.0158	uM
(2R,3R,4S,5R)-2-[6-[(3-chlorophenyl)methylsulfanyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol	219062: Displacement of 5-(SAENTA)-X8-fluorescein from K562 cell nucleoside transporter	ki	0.0160	uM

CTD chemical–gene interactions

97 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Gemcitabine	decreases reaction, increases uptake, increases reaction, increases expression, increases response to substance (+2 more)	9
4-nitrobenzylthioinosine	affects cotreatment, decreases reaction, increases uptake, decreases response to substance, increases reaction (+1 more)	5
Dipyridamole	decreases reaction, increases uptake, affects cotreatment, increases reaction, decreases activity (+1 more)	5
Fluorouracil	increases reaction, increases uptake, increases expression, affects response to substance, decreases reaction (+1 more)	4
Uridine	affects cotreatment, decreases reaction, increases uptake, increases reaction	4
Aflatoxin B1	affects expression, decreases methylation, increases expression	4
bisphenol A	affects expression, affects cotreatment, decreases methylation, decreases expression	3
Adenosine	decreases reaction, increases uptake, increases reaction	3
Cisplatin	affects cotreatment, increases expression, decreases expression, affects response to substance	3
Estradiol	affects cotreatment, increases expression	3
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	3
Tretinoin	affects cotreatment, increases expression, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
Acrolein	decreases expression, increases abundance, affects cotreatment	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	2
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	2
Dilazep	decreases reaction, increases uptake	2
Doxorubicin	affects expression, affects response to substance	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
deoxynivalenol	decreases expression	1

ChEMBL screening assays

49 unique, capped per target: 38 binding, 9 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1030589	Binding	Inhibition of human ENT1	CoMFA and CoMSIA 3D-QSAR studies on S(6)-(4-nitrobenzyl)mercaptopurine riboside (NBMPR) analogs as inhibitors of human equilibrative nucleoside transporter 1 (hENT1). — Bioorg Med Chem Lett
CHEMBL3528986	ADMET	Drug transport in yeast assessed as recombinant human ENT1-mediated uptake at 1 uM measured over 2 to 60 mins by scintillation counting analysis in presence of uridine	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
CHEMBL5209596	Functional	Inhibition of the equilibrative nucleoside transporter (ENT1, SLC29A1) as assessed by GPCR-mediated changes in cell morphology using the impedance-based transporter activity through receptor activation (TRACT) assay (PubChem AID: 1745861)	Label-free detection of transporter activity via GPCR signalling in living cells: A case for SLC29A1, the equilibrative nucleoside transporter 1 — Sci Rep

Cellosaurus cell lines

8 cell lines: 5 cancer cell line, 3 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D2D3	Abcam HCT 116 SLC29A1 KO	Cancer cell line	Male
CVCL_D2P6	Abcam THP-1 SLC29A1 KO	Cancer cell line	Male
CVCL_D4E7	HEK-SLC29A1-KO-c2	Transformed cell line	Female
CVCL_D4E8	HEK-SLC29A1-KO-c3	Transformed cell line	Female
CVCL_D4KY	HCT116-SLC29A1-KO-c10	Cancer cell line	Male
CVCL_D4KZ	HCT116-SLC29A1-KO-c4	Cancer cell line	Male
CVCL_D9RV	Ubigene HEK293 SLC29A1 KO	Transformed cell line	Female
CVCL_TM74	HAP1 SLC29A1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02969174	Not specified	APPROVED_FOR_MARKETING	Establish a Non-invasive Prenatal Genotyping and Extraction Technology to Diagnose and Treat the HDN.
NCT07371520	Not specified	NOT_YET_RECRUITING	Application of Quantitative Hemorrhage Detection in Fetomaternal Hemorrhage Syndrome for the Diagnosis of Hemolytic Disease of the Newborn