NT5E

Summary

NT5E (5’-nucleotidase ecto, HGNC:8021) is a protein-coding gene on chromosome 6q14.3, encoding 5’-nucleotidase (P21589). Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, with AMP being the preferred substrate. In precision oncology, NT5E Overexpression confers sensitivity to Cetuximab in Colorectal Cancer (CIViC Level B).

The protein encoded by this gene is a plasma membrane protein that catalyzes the conversion of extracellular nucleotides to membrane-permeable nucleosides. The encoded protein is used as a determinant of lymphocyte differentiation. Defects in this gene can lead to the calcification of joints and arteries. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4907 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary arterial and articular multiple calcification syndrome (Strong, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 124 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 15
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_002526

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8021
Approved symbol	NT5E
Name	5’-nucleotidase ecto
Location	6q14.3
Locus type	gene with protein product
Status	Approved
Aliases	CD73, eN, eNT, CALJA
Ensembl gene	ENSG00000135318
Ensembl biotype	protein_coding
OMIM	129190
Entrez	4907

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000257770, ENST00000369646, ENST00000369651, ENST00000416334, ENST00000437581, ENST00000880505, ENST00000880506, ENST00000880507, ENST00000954716, ENST00000954717

RefSeq mRNA: 2 — MANE Select: NM_002526 NM_001204813, NM_002526

CCDS: CCDS5002, CCDS56439

Canonical transcript exons

ENST00000257770 — 9 exons

Exon	Start	End
ENSE00000918638	85485235	85485432
ENSE00000918639	85487335	85487489
ENSE00000918640	85489494	85489599
ENSE00000918641	85490508	85490657
ENSE00000918642	85491977	85492177
ENSE00001853124	85493841	85495784
ENSE00002430594	85467060	85467282
ENSE00002533809	85471237	85471425
ENSE00003847261	85450083	85450478

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 97.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 92.3698 / max 1223.7913, expressed in 1492 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68803	71.8965	1448
68804	10.0301	1098
68800	7.5798	956
68801	1.0244	469
68802	0.5795	379
68799	0.5131	326
68812	0.4441	247
68813	0.2140	74
68798	0.0885	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.96	gold quality
calcaneal tendon	UBERON:0003701	97.04	gold quality
jejunal mucosa	UBERON:0000399	96.12	gold quality
synovial joint	UBERON:0002217	95.99	gold quality
cartilage tissue	UBERON:0002418	94.82	gold quality
smooth muscle tissue	UBERON:0001135	94.50	gold quality
endocervix	UBERON:0000458	94.29	gold quality
tendon	UBERON:0000043	94.01	gold quality
endometrium	UBERON:0001295	93.76	gold quality
tendon of biceps brachii	UBERON:0008188	93.54	gold quality
germinal epithelium of ovary	UBERON:0001304	93.40	gold quality
endometrium epithelium	UBERON:0004811	93.32	gold quality
tibia	UBERON:0000979	92.85	gold quality
decidua	UBERON:0002450	92.69	gold quality
myometrium	UBERON:0001296	92.41	gold quality
popliteal artery	UBERON:0002250	92.19	gold quality
tibial artery	UBERON:0007610	92.19	gold quality
rectum	UBERON:0001052	92.17	gold quality
layer of synovial tissue	UBERON:0007616	92.17	gold quality
uterus	UBERON:0000995	92.14	gold quality
aorta	UBERON:0000947	91.97	gold quality
placenta	UBERON:0001987	91.88	gold quality
ascending aorta	UBERON:0001496	91.77	gold quality
thoracic aorta	UBERON:0001515	91.73	gold quality
descending thoracic aorta	UBERON:0002345	91.73	gold quality
artery	UBERON:0001637	91.71	gold quality
right coronary artery	UBERON:0001625	91.68	gold quality
body of uterus	UBERON:0009853	91.68	gold quality
duodenum	UBERON:0002114	91.58	gold quality
ectocervix	UBERON:0012249	91.19	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	246.42
E-ANND-3	yes	13.59
E-GEOD-137537	no	602.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, FOXO3, GFI1, HIF1A, HNF1A, JUN, LEF1, SP1, STAT3, TCF7, ZNF263

miRNA regulators (miRDB)

118 targeting NT5E, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-22-3P	99.93	68.13	917

Literature-anchored findings (GeneRIF, showing 40)

• Review: Ecto-5’-nucleotidase in B-cell chronic lymphocytic leukemia (PMID:12000134)
• Regulation of ecto-5’-nucleotidase by TNF-alpha in human endothelial cells. (PMID:12030367)
• a critical enzyme responsible for the generation of adenosine (PMID:14578500)
• Review defines glycosylphosphatidylinositol-anchored 5’-nucleotidase as an extracellular, raft-associated enzyme responsible for conversion of extracellular adenosine triphosphate (ATP) into adenosine. (PMID:16709165)
• Expression of ecto-5’-nucleotidase in melanoma correlates with a number of metastasis-related markers and thus may have a function in this process. (PMID:16718268)
• Gliclazide inhibits the activity of lymphocyte ecto-5’-nucleotidase and decreases the concentration of adenosine at the cell surface. (PMID:16735966)
• CD73 is coexpressed with metastasis promoting antigens in human melanoma cells (PMID:17065075)
• CD73 may accelerate the growth of breast cancer by stimulating cell proliferation and tumor angiogenesis. (PMID:17487388)
• CD73 may facilitate the adhesion, migration and invasion of human breast cancer cells through its enzyme activity of generating adenosine (PMID:17671792)
• CD73 expression on central nervous system (CNS) microvasculature was confirmed with stainings of frozen tissue sections of multiple sclerosis brain samples taken at autopsy (PMID:17911479)
• eN is a novel and specific receptor for tenascin C (PMID:18062933)
• inhibition of TRAIL signaling works through interaction of CD73 with death receptor 5, as CD73 and death receptor 5 could be coimmunoprecipitated and were shown to be colocalized in the plasma membrane by confocal microscopy (PMID:18566412)
• Ecto-5’-nucleotidase/CD73 may regulate the extracellular adenosine 5’-monophosphate (AMP) and adenosine levels. (PMID:18636315)
• Data show that in varicocele patients, 5’-nucleotidase activity is decreased in seminal plasma and spermatozoa. (PMID:18787389)
• PMNs facilitate translocation across human epithelium and alter fluid homeostasis via epithelial cell-expressed NT5E. (PMID:18924612)
• CD73 plays a critical role by suppressing transendothelial leukocyte trafficking through its enzymatic activity and mitigates inflammatory and immune sequelae of cardiac transplantation via the adenosine 2B receptor. (PMID:19008478)
• CD73 expression can be modulated within minutes following exposure of HUVEC to lysophosphatidylcholine, and this response may be mediated by PKC (PMID:20476579)
• CD73 plays an important role in breast cancer growth by affecting cell cycle progression and apoptosis. (PMID:20874842)
• Studies indicate that it remains unclear whether interruption of IFNalphaA and IL-10 signaling in the absence of CD73 activity results from a deficiency of its product adenosine or an accumulation of its substrate nucleotides. (PMID:21057730)
• Abnormal expression of CD(73) in Treg cells may participate in the pathogenesis of systemic lupus erythematosus. (PMID:21092450)
• We identified mutations in NT5E in members of three families with symptomatic arterial and joint calcifications. This gene encodes CD73, which converts AMP to adenosine. (PMID:21288095)
• CD73 is expressed on a subpopulation of afferent lymph vessels but is absent on efferent lymphatics, unlike LYVE-1 and podoplanin, which are expressed on both types of lymphatics. (PMID:21346249)
• the ectonucleotidases CD39 and CD73 and ADORA2A appear as possible targets for novel treatments in ovarian cancer (PMID:21638125)
• Exosomes from diverse cancer cell types exhibit potent 5’AMP and ATP phosphohydrolytic activity, partly attributed to exosomally expressed CD73 and CD39, which contribute to extracellular adenosine production. (PMID:21677139)
• MSC migration is controlled by CD73 & CD29, which in turn are regulated by mechanical stimulation of cells (PMID:21732280)
• Sequence and structural analysis of H. influenzae NadN led to the discovery that human CD73 is capable of processing both NAD and NMN, therefore disclosing a possible novel function of human CD73 in systemic NAD metabolism. (PMID:21933152)
• CD73-generated extracellular adenosine activates type 1 purinergic A2A receptors that are constitutively expressed by chronic lymphocytic leukemia cells and that are further elevated in proliferating neoplastic cells. (PMID:21998208)
• The expression of CD73 is associated with leukemia subtype, differentiation and development. The higher differentiation of leukemia cells, the lower of CD73 expression in myeloid and B lymphoid leukemia. (PMID:22040959)
• Data show that the alterations in the CD39/CD73 adenosinergic machinery and loss of function in ADA-deficient Tregs provide insights into a predisposition to autoimmunity and the underlying mechanisms causing defective peripheral tolerance in ADA-SCID. (PMID:22184407)
• In multivariate Cox regression analysis, overexpression of CD73 was proven to be an independent prognostic biomarker for colorectal cancer. (PMID:22287455)
• deregulation of NT5E expression in melanoma occurs via epigenetic changes in the NT5E CpG island (PMID:22454080)
• Elevated CD73 expression in breast cancer can predict a good prognosis. However, the actual role of CD73 in cancerogenesis remains unclear and requires further analysis. (PMID:22553809)
• the activity of CD73 to trigger adenosine signaling sustains a chemoresistant phenotype in glioblastoma multiforme cells (PMID:22833450)
• The absence of ecto-5’NT/CD73 in the D283 cell line, a metastatic medulloblastoma phenotype, suggests that high expression levels of this ectonucleotidase could be correlated with a poor prognosis in patients with medulloblastoma. (PMID:23094051)
• Mutations in the underlying disease genes ENPP1, ABCC6, NT5E, and SLC20A2, respectively, lead to arterial media calcification. (PMID:23122642)
• Crystal structures of the dimeric human e5NT reveal an extensive conformational switch between the open and closed forms of the enzyme. (PMID:23142347)
• crystallization and preliminary X-ray crystallographic analysis of an open structural conformation of human e5NT are described. (PMID:23192044)
• Coronary vasodilation to adenine nucleotides is associated with endothelial CD73-dependent production of extracellular adenosine that acts as an endothelium-derived hyperpolarizing factor. (PMID:23288168)
• SNPs at the 5’-nucleotidase and xanthine oxidase genes influence the risk of noncirrhotic portal hypertension in HIV patients treated with didanosine. (PMID:23315321)
• Isoflurane causes TGF-beta1-dependent induction of renal tubular CD73 and adenosine generation to protect against renal ischemia and reperfusion injury. (PMID:23423261)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	nt5e	ENSDARG00000071017
mus_musculus	Nt5e	ENSMUSG00000032420
rattus_norvegicus	Nt5e	ENSRNOG00000011071
drosophila_melanogaster	veil	FBGN0034225
drosophila_melanogaster	CG30103	FBGN0050103
drosophila_melanogaster	NT5E-2	FBGN0050104
drosophila_melanogaster	CG42249	FBGN0259101

Protein

Protein identifiers

5’-nucleotidase — P21589 (reviewed: P21589)

Alternative names: 5’-deoxynucleotidase, Ecto-5’-nucleotidase, IMP-specific 5’-nucleotidase, Thymidylate 5’-phosphatase

All UniProt accessions (4): P21589, H0Y3X5, H0Y7R7, Q96B60

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, with AMP being the preferred substrate. Shows a preference for ribonucleotide monophosphates over their equivalent deoxyribose forms. Other substrates include IMP, UMP, GMP, CMP, dAMP, dCMP, dTMP, NAD and NMN.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane.

Disease relevance. Calcification of joints and arteries (CALJA) [MIM:211800] A condition characterized by adult-onset calcification of the lower extremity arteries, including the iliac, femoral and tibial arteries, and hand and foot capsule joints. Age of onset has been reported as early as the second decade of life, usually involving intense joint pain or calcification in the hands. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by adenosine 5’-(alpha,beta-methylene)-diphosphate (AMPCP).

Similarity. Belongs to the 5’-nucleotidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P21589-1	1	yes
P21589-2	2

RefSeq proteins (2): NP_001191742, NP_002517* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004843	Calcineurin-like_PHP	Domain
IPR006146	5’-Nucleotdase_CS	Conserved_site
IPR006179	5_nucleotidase/apyrase	Family
IPR008334	5’-Nucleotdase_C	Domain
IPR029052	Metallo-depent_PP-like	Homologous_superfamily
IPR036907	5’-Nucleotdase_C_sf	Homologous_superfamily

Pfam: PF00149, PF02872

Enzyme classification (BRENDA):

• EC 3.1.3.5 — 5’-nucleotidase (BRENDA: 107 organisms, 375 substrates, 402 inhibitors, 307 Km, 66 kcat entries)

Substrate kinetics (BRENDA)

39 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5’-AMP	0.0003–23	73
5’-IMP	0.0071–18	49
5’-GMP	0.0064–7.2	29
5’-UMP	0.014–56	27
5’-CMP	0.002–100	19
INOSINE	0.25–10.2	13
5’-DAMP	0.012–35	9
AMP	0.0091–1.49	8
5’-DGMP	0.044–142	7
4-NITROPHENYL PHOSPHATE	0.224–21.78	6
5’-DCMP	0.023–0.75	6
DCMP	0.012–0.193	6
5’-TMP	0.008–0.73	5
5’-XMP	0.065–2.9	5
5’-DTMP	0.008–22	4

Catalyzed reactions (Rhea), 10 shown:

• dTMP + H2O = thymidine + phosphate (RHEA:11080)
• a ribonucleoside 5’-phosphate + H2O = a ribonucleoside + phosphate (RHEA:12484)
• GMP + H2O = guanosine + phosphate (RHEA:27714)
• IMP + H2O = inosine + phosphate (RHEA:27718)
• UMP + H2O = uridine + phosphate (RHEA:29359)
• dCMP + H2O = 2’-deoxycytidine + phosphate (RHEA:29363)
• CMP + H2O = cytidine + phosphate (RHEA:29367)
• dAMP + H2O = 2’-deoxyadenosine + phosphate (RHEA:29371)
• AMP + H2O = adenosine + phosphate (RHEA:29375)
• a 2’-deoxyribonucleoside 5’-phosphate + H2O = a 2’-deoxyribonucleoside + phosphate (RHEA:36167)

UniProt features (96 total): strand 31, helix 22, binding site 20, turn 5, glycosylation site 4, disulfide bond 4, sequence variant 3, site 2, signal peptide 1, chain 1, propeptide 1, lipid moiety-binding region 1, splice variant 1

Structure

Experimental structures (PDB)

51 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6TVE	X-RAY DIFFRACTION	1.05
9HJ4	X-RAY DIFFRACTION	1.06
7PBY	X-RAY DIFFRACTION	1.13
7PB5	X-RAY DIFFRACTION	1.28
7PCP	X-RAY DIFFRACTION	1.38
7PD9	X-RAY DIFFRACTION	1.39
7P9R	X-RAY DIFFRACTION	1.41
7PBA	X-RAY DIFFRACTION	1.42
7PA4	X-RAY DIFFRACTION	1.45
7PBB	X-RAY DIFFRACTION	1.47
6TVG	X-RAY DIFFRACTION	1.48
7QGA	X-RAY DIFFRACTION	1.5
7QGL	X-RAY DIFFRACTION	1.5
4H2G	X-RAY DIFFRACTION	1.55
7P9N	X-RAY DIFFRACTION	1.55
4H1Y	X-RAY DIFFRACTION	1.58
4H2B	X-RAY DIFFRACTION	1.7
7P9T	X-RAY DIFFRACTION	1.79
4H2F	X-RAY DIFFRACTION	1.85
6S7H	X-RAY DIFFRACTION	1.85
6Z9D	X-RAY DIFFRACTION	1.9
6XUE	X-RAY DIFFRACTION	1.94
6XUQ	X-RAY DIFFRACTION	1.97
4H2I	X-RAY DIFFRACTION	2
6TWA	X-RAY DIFFRACTION	2
6S7F	X-RAY DIFFRACTION	2.05
6XUG	X-RAY DIFFRACTION	2.09
6Z9B	X-RAY DIFFRACTION	2.17
4H1S	X-RAY DIFFRACTION	2.2
7QGO	X-RAY DIFFRACTION	2.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21589-F1	91.95	0.86

Antibody-complex structures (SAbDab): 5 — 6HXW, 6VC9, 6VCA, 7BBJ, 8ZNZ

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 (2): 118 (transition state stabilizer); 121 (transition state stabilizer)

Ligand- & substrate-binding residues (20): 243; 354; 354; 390; 390; 395; 395; 417; 417; 500; 500; 506 …

Post-translational modifications (1): 549

Disulfide bonds (4): 51–57, 353–358, 365–387, 476–479

Glycosylation sites (4): 53, 311, 333, 403

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-196807	Nicotinate metabolism
R-HSA-73621	Pyrimidine catabolism
R-HSA-74259	Purine catabolism
R-HSA-9660826	Purinergic signaling in leishmaniasis infection
R-HSA-1430728	Metabolism
R-HSA-15869	Metabolism of nucleotides
R-HSA-1643685	Disease
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-5663205	Infectious disease
R-HSA-8956319	Nucleotide catabolism
R-HSA-9658195	Leishmania infection
R-HSA-9664424	Cell recruitment (pro-inflammatory response)
R-HSA-9824443	Parasitic Infection Pathways

MSigDB gene sets: 442 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, TSUNODA_CISPLATIN_RESISTANCE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_INFLAMMATORY_RESPONSE, REACTOME_PYRIMIDINE_CATABOLISM, AAGTCCA_MIR422B_MIR422A, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS

GO Biological Process (11): AMP catabolic process (GO:0006196), DNA metabolic process (GO:0006259), leukocyte cell-cell adhesion (GO:0007159), response to ATP (GO:0033198), ADP catabolic process (GO:0046032), ATP metabolic process (GO:0046034), adenosine biosynthetic process (GO:0046086), negative regulation of inflammatory response (GO:0050728), calcium ion homeostasis (GO:0055074), inhibition of non-skeletal tissue mineralization (GO:0140928), nucleotide catabolic process (GO:0009166)

GO Molecular Function (9): nucleotide binding (GO:0000166), 5’-deoxynucleotidase activity (GO:0002953), 5’-nucleotidase activity (GO:0008253), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on ester bonds (GO:0016788), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), extracellular exosome (GO:0070062), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Nucleotide catabolism	2
Metabolism	2
Metabolism of water-soluble vitamins and cofactors	1
Cell recruitment (pro-inflammatory response)	1
Metabolism of vitamins and cofactors	1
Disease	1
Metabolism of nucleotides	1
Parasitic Infection Pathways	1
Leishmania infection	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
purine ribonucleotide catabolic process	2
membrane	2
purine ribonucleoside monophosphate catabolic process	1
AMP metabolic process	1
nucleic acid metabolic process	1
cell-cell adhesion	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
purine ribonucleoside diphosphate catabolic process	1
ADP metabolic process	1
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
adenosine metabolic process	1
purine ribonucleoside biosynthetic process	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
tissue homeostasis	1
nucleotide metabolic process	1
nucleoside phosphate catabolic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
5’-nucleotidase activity	1
nucleotidase activity	1
transition metal ion binding	1
protein binding	1
binding	1
catalytic activity	1
hydrolase activity	1
cation binding	1
nuclear lumen	1
cytoplasm	1
cell periphery	1
plasma membrane	1
cell surface	1

Protein interactions and networks

STRING

4140 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NT5E	ENTPD1	P49961	998
NT5E	ENG	P17813	923
NT5E	THY1	P04216	919
NT5E	CD34	P28906	905
NT5E	PTPRC	P08575	892
NT5E	ITGB1	P05556	889
NT5E	CD44	P16070	889
NT5E	ENPP1	P22413	880
NT5E	ADORA2A	P29274	869
NT5E	ALCAM	Q13740	854
NT5E	PECAM1	P16284	824
NT5E	CD19	P15391	816
NT5E	ITGAM	P11215	792
NT5E	MCAM	P43121	778
NT5E	ANPEP	P15144	756

IntAct

41 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
NT5E	RNF24	psi-mi:“MI:0915”(physical association)	0.560
NT5E	ZNRF4	psi-mi:“MI:0915”(physical association)	0.560
NT5E	SCAMP1	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
RAB11A	LANCL1	psi-mi:“MI:2364”(proximity)	0.420
NT5E	ARG2	psi-mi:“MI:0915”(physical association)	0.400
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DDR1		psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
TEX101	ITGB1	psi-mi:“MI:0914”(association)	0.350
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350
CD81	CD276	psi-mi:“MI:0914”(association)	0.350
VPS35		psi-mi:“MI:0914”(association)	0.350
ZBTB18	DNASE1L1	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
NT5E	SCAMP3	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (158): XPO7 (Affinity Capture-MS), CHD1L (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), ATR (Affinity Capture-MS), RPTOR (Affinity Capture-MS), GLMN (Affinity Capture-MS), RDH13 (Affinity Capture-MS), SCAMP1 (Affinity Capture-MS), USP22 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), RFC2 (Affinity Capture-MS), RAB9A (Affinity Capture-MS), DNAAF5 (Affinity Capture-MS), MTOR (Affinity Capture-MS), GHITM (Affinity Capture-MS)

ESM2 similar proteins: A0A2I4HXH5, A5D6U8, B3A0N5, B6EWW8, E0D877, F8S0Z7, O00462, O35409, P05089, P15693, P19492, P21588, P21589, P29240, P31422, P42263, P49614, P49900, P50635, P52307, P70627, P83456, P83852, Q05927, Q14832, Q1ZZH1, Q29444, Q2KJ64, Q4FZV0, Q561R9, Q5R979, Q5RAL3, Q5RFI5, Q5TVM9, Q5XGR8, Q61503, Q641Z7, Q6AYS4, Q6PCE3, Q8CAA7

Diamond homologs: A0A2I4HXH5, B3A0N5, B6EWW8, E0D877, F8S0Z7, O34313, O83142, P21588, P21589, P29240, P44569, P50635, P52307, Q05927, Q5TVM9, Q61503, Q95P65, Q9XZ43, W8EFS0, P07778, P0DJJ5, A9BJC1, P08331, P22848, P26265, P44764, P53052, Q8DFG4

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
HIF1A	“up-regulates quantity by expression”	NT5E	“transcriptional regulation”
TTK	“up-regulates activity”	NT5E	phosphorylation
NT5E	“up-regulates quantity”	adenosine	“chemical modification”
NT5E	“down-regulates quantity”	AMP	“chemical modification”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	88
Likely benign	16
Benign	9

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
29687	NM_002526.4(NT5E):c.662C>A (p.Ser221Ter)	Pathogenic
29688	NM_002526.4(NT5E):c.1073G>A (p.Cys358Tyr)	Pathogenic
2633543	NM_002526.4(NT5E):c.1428C>A (p.Cys476Ter)	Likely pathogenic
29689	NM_002526.4(NT5E):c.1608dup (p.Val537fs)	Likely pathogenic

SpliceAI

1242 predictions. Top by Δscore:

Variant	Effect	Δscore
6:85450477:TGG:T	donor_loss	1.0000
6:85450479:G:GA	donor_loss	1.0000
6:85450480:T:G	donor_loss	1.0000
6:85467055:TCTAG:T	acceptor_loss	1.0000
6:85467057:TAG:T	acceptor_loss	1.0000
6:85467058:A:AG	acceptor_gain	1.0000
6:85467058:AG:A	acceptor_gain	1.0000
6:85467059:G:GG	acceptor_gain	1.0000
6:85467059:GG:G	acceptor_gain	1.0000
6:85467059:GGCAC:G	acceptor_gain	1.0000
6:85471235:A:AG	acceptor_gain	1.0000
6:85471235:AG:A	acceptor_gain	1.0000
6:85471235:AGG:A	acceptor_gain	1.0000
6:85471236:G:A	acceptor_loss	1.0000
6:85471236:G:GC	acceptor_gain	1.0000
6:85471236:GG:G	acceptor_gain	1.0000
6:85471236:GGG:G	acceptor_gain	1.0000
6:85471236:GGGA:G	acceptor_gain	1.0000
6:85471236:GGGAC:G	acceptor_gain	1.0000
6:85471421:CACAG:C	donor_loss	1.0000
6:85471422:ACAG:A	donor_loss	1.0000
6:85471424:AG:A	donor_loss	1.0000
6:85471425:GG:G	donor_loss	1.0000
6:85471427:T:A	donor_loss	1.0000
6:85485233:A:AG	acceptor_gain	1.0000
6:85485234:G:GG	acceptor_gain	1.0000
6:85485234:GGC:G	acceptor_gain	1.0000
6:85485234:GGCA:G	acceptor_gain	1.0000
6:85485428:TGAAG:T	donor_gain	1.0000
6:85485429:GAAG:G	donor_gain	1.0000

AlphaMissense

3759 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:85450393:A:T	D85V	0.999
6:85450246:A:T	D36V	0.998
6:85450393:A:C	D85A	0.998
6:85450416:T:C	F93L	0.998
6:85450418:C:A	F93L	0.998
6:85450418:C:G	F93L	0.998
6:85450246:A:C	D36A	0.997
6:85467071:T:A	N117K	0.997
6:85467071:T:G	N117K	0.997
6:85467072:C:G	H118D	0.997
6:85467074:T:A	H118Q	0.997
6:85467074:T:G	H118Q	0.997
6:85487473:T:C	L363P	0.997
6:85487484:G:C	A367P	0.997
6:85450244:C:A	N35K	0.996
6:85450244:C:G	N35K	0.996
6:85450247:C:A	D36E	0.996
6:85450247:C:G	D36E	0.996
6:85450258:G:C	R40P	0.996
6:85450393:A:G	D85G	0.996
6:85450394:C:A	D85E	0.996
6:85450394:C:G	D85E	0.996
6:85450404:G:C	G89R	0.996
6:85467067:G:T	G116V	0.996
6:85467073:A:C	H118P	0.996
6:85467141:A:C	S141R	0.996
6:85467143:T:A	S141R	0.996
6:85467143:T:G	S141R	0.996
6:85490609:A:C	S438R	0.996
6:85490611:C:A	S438R	0.996

dbSNP variants (sampled 300 via entrez): RS1000056641 (6:85450378 T>G), RS1000059895 (6:85457009 G>T), RS1000169347 (6:85450697 G>A,T), RS1000219742 (6:85463740 G>A), RS1000233406 (6:85474185 T>G), RS1000241264 (6:85456811 G>A,T), RS1000356592 (6:85463385 A>C,G), RS1000424526 (6:85470527 T>C), RS1000498416 (6:85488070 G>C), RS1000528088 (6:85457068 T>C), RS1000653286 (6:85494886 A>G), RS1000697924 (6:85468471 T>C), RS1000702311 (6:85494534 C>T), RS1000902664 (6:85468485 G>A,T), RS1000916528 (6:85475636 G>A)

Disease associations

OMIM: gene MIM:129190 | disease phenotypes: MIM:211800

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary arterial and articular multiple calcification syndrome	Strong	Autosomal recessive

Mondo (2): hereditary arterial and articular multiple calcification syndrome (MONDO:0008895), intellectual disability (MONDO:0001071)

Orphanet (2): Hereditary arterial and articular multiple calcification syndrome (Orphanet:289601), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001717	Coronary artery calcification
HP:0003207	Arterial calcification
HP:0004417	Intermittent claudication
HP:0005116	Arterial tortuosity
HP:0005645	Intervertebral disk calcification
HP:0011025	Abnormal cardiovascular system physiology
HP:0011986	Ectopic ossification
HP:0012101	Decreased serum creatinine
HP:0025015	Abnormal vascular morphology
HP:0025324	Arterial occlusion
HP:0025477	Periarticular calcification
HP:0031303	Femoral arterial calcification
HP:0031304	Iliac arterial calcification
HP:0031305	Tibial arterial calcification

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001217_27	Metabolic traits	7.000000e-13
GCST006993_8	Hippocampal volume in Alzheimer’s disease dementia	8.000000e-07
GCST010057_4	Lung function	2.000000e-06
GCST012020_117	Serum metabolite levels	9.000000e-15
GCST012020_118	Serum metabolite levels	9.000000e-14
GCST012020_119	Serum metabolite levels	6.000000e-13
GCST012020_7	Serum metabolite levels	5.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004725	metabolite measurement
EFO:0005035	hippocampal volume
EFO:0004312	vital capacity

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C565891	Calcification of Joints and Arteries (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5957 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 220,396 (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
CHEMBL1568	FLUDARABINE	3	101,629
CHEMBL50	QUERCETIN	3	74,559
CHEMBL2105120	FTIVAZIDE	2	118
CHEMBL4471306	QUEMLICLUSTAT	2	490
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL269277	BETULINIC ACID	1	20,430
CHEMBL4792487	LY-3475070	1	22

Clinical evidence (CIViC)

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

Variant	Therapy	Indication	Effect	Level	CIViC
NT5E Overexpression	Cetuximab	Colorectal Cancer	Sensitivity/Response	CIViC B	EID730

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9450278	NT5E		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Adenosine turnover

Most potent curated ligand interactions (10 total), top 10:

Ligand	Action	Affinity	Parameter
oleclumab	Binding	11.38	pKd
quemliclustat	Inhibition	11.3	pKi
dalutrafusp alfa	Binding	10.16	pKd
compound 49 [PMID: 36529947]	Inhibition	9.77	pIC50
αβ-methyleneADP	Inhibition	8.7	pIC50
compound 15 [PMID: 32045236]	Inhibition	8.44	pKi
mupadolimab	Inhibition	8.15	pKd
ORIC-533	Inhibition	8.0	pIC50
quercetin	Inhibition	7.34	pKi
PSB-0963	Inhibition	6.82	pKi

Binding affinities (BindingDB)

35 measured of 70 human assays (147 total across all organisms); most potent 35 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3-(4-phenylmethoxyphenyl)-2-(tetrazolidin-5-yl)propanoic acid	IC50	29 nM	US-10570167: Ectonucleotidase inhibitors and methods of use thereof
2-[[(2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methoxy]-2-[[4-(3,5-dimethyl-1H-pyrazol-4-yl)phenyl]methyl]propanedioic acid	IC50	34 nM	US-10570167: Ectonucleotidase inhibitors and methods of use thereof
2-[[(2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-3-hydroxyoxolan-2-yl]methoxy]-2-[[4-(5-methyl-1H-pyrazol-4-yl)phenyl]methyl]propanedioic acid	IC50	48 nM	US-10570167: Ectonucleotidase inhibitors and methods of use thereof
2-[4-[2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-2-carboxy-2-(tetrazolidin-5-yl)ethyl]phenyl]benzoic acid	IC50	53 nM	US-10570167: Ectonucleotidase inhibitors and methods of use thereof
[[(2R,4S,5R)-5-[6-[[2-(1-adamantyl)acetyl]amino]-2-chloropurin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	IC50	55 nM	US-20230295213: CD73 INHIBITORS AND PHARMACEUTICAL USES THEREOF
[[(2R,4S,5R)-5-[2-chloro-6-[2-oxo-2-[[(1R,4R)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl]oxy]ethyl]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	IC50	55 nM	US-20230295213: CD73 INHIBITORS AND PHARMACEUTICAL USES THEREOF
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-2-(2H-tetrazol-5-yl)-3-[3-(trifluoromethoxy)phenyl]propanoic acid	IC50	118 nM	US-10570167: Ectonucleotidase inhibitors and methods of use thereof
(E)-N’-(1-(3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1yl)ethylidene)isonicotino hydrazide (3j)	IC50	190 nM
(E)-N’-(Pyridin-3’-ylmethylene)isonicotinohydrazide (3i)	IC50	210 nM
US10472364, Compound 54	IC50	220 nM	US-10472364: Ectonucleotidase inhibitors and methods of use thereof
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-2-(tetrazolidin-5-yl)-3-thiophen-3-ylpropanoic acid	IC50	227 nM	US-10570167: Ectonucleotidase inhibitors and methods of use thereof
(E)-N’-(4’-Bromobenzylidene)isonicotinohydrazide (3b)	IC50	230 nM
5-(5,7-dimethyl-6-oxo-imidazo[4,5-c]pyridazin-3-yl)-1H-pyrimidine-2,4-dione	IC50	254 nM	US-20260001884: Heterocycle compounds for the treatment of cancer
5-(5-isopropyl-7-methyl-6-oxo-imidazo[4.5-]pyridazin-3-yl)-1H-pyrimidine-2,4-dione	IC50	267 nM	US-20260001884: Heterocycle compounds for the treatment of cancer
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-2-(2H-tetrazol-5-yl)-3-[4-(trifluoromethoxy)phenyl]propanoic acid	IC50	273 nM	US-10570167: Ectonucleotidase inhibitors and methods of use thereof
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-2-(tetrazolidin-5-yl)-3-[4-(trifluoromethyl)phenyl]propanoic acid	IC50	300 nM	US-10570167: Ectonucleotidase inhibitors and methods of use thereof
4-[2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-2-carboxy-2-(2H-tetrazol-5-yl)ethyl]thiophene-2-carboxylic acid	IC50	386 nM	US-10570167: Ectonucleotidase inhibitors and methods of use thereof
US10472364, Compound 53	IC50	448 nM	US-10472364: Ectonucleotidase inhibitors and methods of use thereof
5-(5-methyl-6-oxo-7H-imidazo[4,5-c]pyridazin-3-yl)-1H-pyrimidine-2,4-dione	IC50	622 nM	US-20260001884: Heterocycle compounds for the treatment of cancer
(E)-N’-(4’-Hydroxy-3-methoxybenzylidene)isonicotinohydrazide (3g)	IC50	680 nM
US10472364, Compound 64	IC50	860 nM	US-10472364: Ectonucleotidase inhibitors and methods of use thereof
CHEMBL5403535	IC50	860 nM
US10472364, Compound 43	IC50	1040 nM	US-10472364: Ectonucleotidase inhibitors and methods of use thereof
2-[[(2R,3R,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3-phenyl-2-(2H-tetrazol-5-yl)propanoic acid	IC50	1110 nM	US-10570167: Ectonucleotidase inhibitors and methods of use thereof
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3-pyridin-3-yl-2-(2H-tetrazol-5-yl)propanoic acid	IC50	1180 nM	US-10570167: Ectonucleotidase inhibitors and methods of use thereof
(E)-N’-(2’-hydroxybenzylidene)isonicotinohydrazide (3e)	IC50	1340 nM
(E)-N’-(4’-Chlorobenzylidene)isonicotinohydrazide (3a)	IC50	1670 nM
(E)-N’-(3’-Nitrobenzylidene)isonicotinohydrazide (3f)	IC50	1900 nM
US10472364, Compound 50	IC50	1910 nM	US-10472364: Ectonucleotidase inhibitors and methods of use thereof
(E)-N’-(Pyridin-4’-ylmethylene)isonicotinohydrazide (3h)	IC50	2120 nM
4-[2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-2-carboxy-2-(2H-tetrazol-5-yl)ethyl]benzoic acid	IC50	2430 nM	US-10570167: Ectonucleotidase inhibitors and methods of use thereof
CHEMBL5415729	IC50	4800 nM
(E)-N’-(4’-Fluorobenzylidene)isonicotinohydrazide (3c)	IC50	6760 nM
(E)-N’-(4’-Methoxybenzylidene)isonicotinohydrazide (3d)	IC50	13800 nM
CHEMBL5428963	IC50	19000 nM

ChEMBL bioactivities

1448 potent at pChembl≥5 of 1520 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL4761506
10.96	IC50	0.011	nM	QUEMLICLUSTAT
10.89	IC50	0.013	nM	CHEMBL5431118
10.70	IC50	0.02	nM	CHEMBL6162112
10.70	IC50	0.02	nM	CHEMBL6152291
10.68	IC50	0.021	nM	CHEMBL4761506
10.57	IC50	0.027	nM	CHEMBL4749428
10.55	IC50	0.028	nM	CHEMBL4776758
10.51	IC50	0.031	nM	CHEMBL4746184
10.51	IC50	0.031	nM	CHEMBL4740465
10.49	IC50	0.032	nM	CHEMBL4797225
10.42	Ki	0.038	nM	CHEMBL5423436
10.40	IC50	0.04	nM	CHEMBL6150713
10.40	IC50	0.04	nM	CHEMBL6160794
10.40	IC50	0.04	nM	CHEMBL6167368
10.39	IC50	0.041	nM	QUEMLICLUSTAT
10.37	IC50	0.043	nM	QUEMLICLUSTAT
10.35	IC50	0.045	nM	CHEMBL4743437
10.30	IC50	0.05	nM	CHEMBL5431118
10.30	IC50	0.05	nM	CHEMBL6035583
10.30	IC50	0.05	nM	CHEMBL6170363
10.29	IC50	0.051	nM	CHEMBL5431118
10.28	IC50	0.052	nM	CHEMBL4790144
10.28	IC50	0.053	nM	CHEMBL4743437
10.24	IC50	0.058	nM	CHEMBL4745002
10.22	IC50	0.06	nM	CHEMBL6026050
10.15	IC50	0.07	nM	CHEMBL4784155
10.13	IC50	0.074	nM	CHEMBL5984330
10.10	IC50	0.08	nM	CHEMBL6062089
10.02	IC50	0.095	nM	CHEMBL4777161
10.00	IC50	0.1	nM	CHEMBL5404625
10.00	IC50	0.1	nM	CHEMBL5423436
9.96	Ki	0.11	nM	CHEMBL5423436
9.96	IC50	0.11	nM	CHEMBL5899531
9.96	IC50	0.11	nM	CHEMBL5929751
9.94	IC50	0.115	nM	CHEMBL4761506
9.92	IC50	0.12	nM	CHEMBL4753354
9.89	IC50	0.13	nM	CHEMBL5827587
9.89	IC50	0.13	nM	CHEMBL5786397
9.85	IC50	0.14	nM	CHEMBL5923677
9.82	IC50	0.15	nM	CHEMBL4763896
9.82	IC50	0.15	nM	CHEMBL4758486
9.82	IC50	0.15	nM	CHEMBL5423436
9.82	IC50	0.15	nM	CHEMBL5809627
9.80	IC50	0.16	nM	CHEMBL5844303
9.77	IC50	0.17	nM	CHEMBL5423436
9.74	IC50	0.18	nM	CHEMBL5423436
9.70	IC50	0.2	nM	CHEMBL4744502
9.70	IC50	0.2	nM	CHEMBL5398484
9.70	IC50	0.2	nM	CHEMBL5828700

PubChem BioAssay actives

544 with measured affinity, of 851 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
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-1-(2-fluorophenyl)ethyl]amino]pyrazolo[5,4-b]pyridin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1605331: Inhibition of human CD73	ki	<0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-1-(3-fluorophenyl)ethyl]amino]pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-1-phenylethyl]amino]pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[2-chloro-4-[[(1S)-1-(4-fluorophenyl)ethyl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-1-(4-fluorophenyl)ethyl]amino]pyrazolo[5,4-b]pyridin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674272: Inhibition of CD73 in human CD8-positive T cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 2.5 hrs by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[2-chloro-4-[[(1S)-1-(2-fluorophenyl)ethyl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
[[(2R,3S,4R,5R)-5-[2-chloro-4-[[(1S)-1-(3-fluorophenyl)ethyl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	<0.0001	uM
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]-2-[[4-(2-oxo-1,3-diazinan-1-yl)phenyl]methyl]propanedioic acid	1964441: Competitive inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells assessed as inhibition constant incubated for 1 hr by malachite green based spectrophotometer assay	ki	<0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1R)-1-(2-fluorophenyl)ethyl]amino]pyrazolo[5,4-b]pyridin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	2007820: Binding affinity to C-terminal His6-tagged human recombinant CD73 in HEK293 cells assessed as inhibition constant	ki	<0.0001	uM
[(2R,3S,4R,5R)-5-[5-chloro-7-[[(1S)-1-(2-fluorophenyl)ethyl]amino]imidazo[4,5-b]pyridin-3-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	2132855: Binding affinity to human recombinant CD73 assessed as inhibition constant	ki	<0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1R)-1-phenylethyl]amino]pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
[[(2R,3S,4R,5R)-5-[4-(benzylamino)-6-chloropyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-1-(2-fluorophenyl)ethyl]amino]pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
[[(2R,3R,4S,5R)-5-[2-chloro-6-[cyclopentyl(methyl)amino]purin-9-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-1-(4-fluorophenyl)ethyl]amino]pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
[[(2R,3S,4R,5R)-5-[2-chloro-6-[cyclopentyl(methyl)amino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
[[(2R,3R,4S,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0001	uM
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]-2-[[4-(2-oxo-1H-pyridin-3-yl)phenyl]methyl]propanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0001	uM
[(2R,3S,4R,5R)-5-(6-chloro-4-spiro[1,2-dihydroindene-3,3’-azetidine]-1’-ylpyrazolo[5,4-d]pyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxymethylphosphonic acid	2007821: Inhibition of human CD73	ic50	0.0001	uM
[[(2R,3S,4R,5R)-5-[2-chloro-6-(cyclopentylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0002	uM
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]-2-[[4-(2-carboxyphenyl)phenyl]methyl]propanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0002	uM
[(2R)-2-[[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy]-1-hydroxy-3-methoxypropan-2-yl]phosphonic acid	1724305: Inhibition of CD73 in human CD8+ T-cells assessed as reduction in AMP-induced ADO expression preincubated for 15 mins followed by AMP addition and measured after 1 hr by LC-MS/MS analysis	ec50	0.0002	uM
[[(2R,3S,4R,5R)-5-[6-(benzylamino)-2-chloropurin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0003	uM
2-benzyl-2-[[(2R,3S,4R,5R)-5-(2-chloro-6-thiophen-2-ylpurin-9-yl)-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]propanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0003	uM
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]-2-[[4-(2-oxopiperidin-1-yl)phenyl]methyl]propanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0003	uM
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]-2-[(4-phenylphenyl)methyl]propanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0003	uM
[[(2R,3S,4R,5R)-5-[6-[benzyl(methyl)amino]-2-chloropurin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1605331: Inhibition of human CD73	ki	0.0003	uM
[[(2R,3S,4R,5R)-5-[2-chloro-6-[[(1S)-1-phenylethyl]amino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0003	uM
[(2R,3S,4R,5R)-5-[2-chloro-6-[(2-fluorophenyl)methyl-methylamino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	2132855: Binding affinity to human recombinant CD73 assessed as inhibition constant	ki	0.0003	uM
[[(2R,3R,4S,5R)-5-[2-chloro-6-(cyclopentylamino)purin-9-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0004	uM
[(2R,3S,4R,5R)-5-[6-(benzylamino)-2-chloropurin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate	1744449: Inhibition of human CD73 expressed in CHO cells incubated for 60 mins before addition of AMP and further incubated for 60 mins by colorimetric assay	ic50	0.0004	uM
bis(N,N-diethylethanamine);[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[(4Z)-4-[(4-iodophenyl)methoxyimino]-3-methyl-2-oxopyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1819263: Inhibition of human soluble CD73 assessed as inhibition constant	ki	0.0004	uM
[[(2R,3S,4R,5R)-5-[(4Z)-4-[(4-bromophenyl)methoxyimino]-3-methyl-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid;bis(N,N-diethylethanamine)	1819263: Inhibition of human soluble CD73 assessed as inhibition constant	ki	0.0004	uM
2-[[(2R,3S,4R,5R)-5-(6-amino-2-chloropurin-9-yl)-3-(2-cyclopropylethynyl)-3,4-dihydroxyoxolan-2-yl]methoxy]-2-benzylpropanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0005	uM
[2-[[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy]-1-hydroxy-3-methoxypropan-2-yl]phosphonic acid	1724307: Inhibition of human C-terminal His6-tagged CD73 expressed in CHO cells preincubated for 15 mins followed by AMP addition and measured after 10 mins by malachite green reagent based assay	ic50	0.0005	uM
[(2R)-2-[[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy]-1-hydroxypropan-2-yl]phosphonic acid	1724307: Inhibition of human C-terminal His6-tagged CD73 expressed in CHO cells preincubated for 15 mins followed by AMP addition and measured after 10 mins by malachite green reagent based assay	ic50	0.0005	uM
[[(2R,3S,4R,5R)-5-[6-chloro-4-[[(1S)-2,3-dihydro-1H-inden-1-yl]-methylamino]pyrazolo[5,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1724307: Inhibition of human C-terminal His6-tagged CD73 expressed in CHO cells preincubated for 15 mins followed by AMP addition and measured after 10 mins by malachite green reagent based assay	ic50	0.0005	uM
bis(N,N-diethylethanamine);[[(2R,3S,4R,5R)-3,4-dihydroxy-5-[(4Z)-3-methyl-2-oxo-4-[[4-(pentafluoro-lambda6-sulfanyl)phenyl]methoxyimino]pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1819263: Inhibition of human soluble CD73 assessed as inhibition constant	ki	0.0005	uM
[[(2R,3R,4S,5R)-5-[6-(cyclopentylamino)-2-(methoxymethyl)purin-9-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0006	uM
[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethylphosphonic acid	1744447: Inhibition of CD73 in human SK-OV-3 cells incubated for 60 mins before addition of AMP and further incubated for 60 mins by colorimetric assay	ic50	0.0006	uM
2-benzyl-2-[[(2R,3S,4R,5R)-5-[2-chloro-6-(3-hydroxyazetidin-1-yl)purin-9-yl]-3-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy]propanedioic acid	1964387: Inhibition of soluble C-terminal 6His-tagged recombinant human CD73 (27 to 547 residues) expressed in CHO cells incubated for 1 hr by malachite green based spectrophotometer assay	ic50	0.0006	uM
[2-[[(2R,3S,4R,5R)-5-[6-chloro-4-(cyclopentylamino)pyrazolo[3,4-d]pyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy]-1,3-dihydroxypropan-2-yl]phosphonic acid	1724307: Inhibition of human C-terminal His6-tagged CD73 expressed in CHO cells preincubated for 15 mins followed by AMP addition and measured after 10 mins by malachite green reagent based assay	ic50	0.0006	uM
[[(2R,3S,4R,5R)-5-[(4Z)-4-[[4-(2-aminoethylcarbamoyl)phenyl]methoxyimino]-3-methyl-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid;bis(N,N-diethylethanamine)	1819263: Inhibition of human soluble CD73 assessed as inhibition constant	ki	0.0006	uM
5-[3-[(1R)-2,2-difluoro-1-phenylethoxy]-1-methylpyrazolo[3,4-c]pyridazin-5-yl]-1H-pyrimidine-2,4-dione	2094800: Inhibition of CD73 in human MDA-MB-231 cells preincubated for 30 mins followed by AMP addition and measured after 45 mins by plate reader analysis	ic50	0.0006	uM
[[(2R,3S,4R,5R)-5-[2-chloro-6-(propan-2-ylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0007	uM
[[(2R,3R,4S,5R)-5-[6-(benzylamino)-2-chloropurin-9-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0007	uM
[[(2R,3S,4R,5R)-5-[2-chloro-6-[[(1R)-1-phenylethyl]amino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid	1674269: Inhibition of human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by PiColorLock gold reagent based colorimetric assay	ic50	0.0007	uM
[[(2R,3S,4R,5R)-5-[(4Z)-4-[(4-chlorophenyl)methoxyimino]-3-methyl-2-oxopyrimidin-1-yl]-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid;bis(N,N-diethylethanamine)	1819263: Inhibition of human soluble CD73 assessed as inhibition constant	ki	0.0007	uM
5-[3-[(1R)-2,2-difluoro-1-(5-fluoro-2-pyridinyl)ethoxy]-1-methylpyrazolo[3,4-c]pyridazin-5-yl]-1H-pyrimidine-2,4-dione	2094800: Inhibition of CD73 in human MDA-MB-231 cells preincubated for 30 mins followed by AMP addition and measured after 45 mins by plate reader analysis	ic50	0.0007	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, decreases reaction, affects cotreatment, increases expression	5
Tetrachlorodibenzodioxin	affects expression, decreases expression	4
cobaltous chloride	decreases expression, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
Valproic Acid	decreases expression, decreases methylation, increases expression	3
Cyclosporine	affects expression, increases expression	3
bisphenol A	decreases expression, decreases methylation, increases expression	2
sodium arsenite	decreases expression, increases expression	2
chloropicrin	affects expression, decreases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Formaldehyde	decreases expression, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Quercetin	decreases expression, decreases activity	2
Medroxyprogesterone Acetate	affects cotreatment, increases expression, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
beta-Naphthoflavone	decreases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	decreases expression	1
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
deoxynivalenol	decreases expression	1
lead acetate	increases expression	1
sodium arsenate	increases expression, increases abundance	1

ChEMBL screening assays

181 unique, capped per target: 181 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1042900	Binding	Activity at ecto-5’-nucleotidase	Nucleoside-5’-monophosphates as prodrugs of adenosine A2A receptor agonists activated by ecto-5’-nucleotidase. — J Med Chem

Cellosaurus cell lines

5 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell, 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1CI	Abcam A-431 NT5E KO	Cancer cell line	Female
CVCL_B7V4	Abcam A-375 NT5E KO	Cancer cell line	Female
CVCL_C9M7	BFVSBi001-A	Induced pluripotent stem cell	Male
CVCL_E6RF	Genomeditech CHO-K1 H_NT5E(CD73)	Spontaneously immortalized cell line	Female
CVCL_E6UR	Genomeditech HEK-293 H_NT5E(CD73)	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
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