Target Information
Target General Information | Top | |||||
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Target ID |
T58298
(Former ID: TTDR00537)
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Target Name |
Ectonucleoside triphosphate diphosphohydrolase 1 (CD39)
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Synonyms |
NTPDase1; NTPDase 1; Lymphoid cell activation antigen; Ecto-nucleotidase CD-39; Ecto-apyrase; Ecto-ATPase 1; Ecto-ATPDase 1; Ecto-ATP diphosphohydrolase 1; Ecto-ATP diphosphohydrolase; CD39 antigen; ATPDase
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Gene Name |
ENTPD1
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Lymphoma [ICD-11: 2A80-2A86] | |||||
2 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
Could also be implicated in the prevention of platelet aggregation by hydrolyzing platelet-activating ADP to AMP. Hydrolyzes ATP and ADP equally well. In the nervous system, could hydrolyze ATP and other nucleotides to regulate purinergic neurotransmission.
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BioChemical Class |
Acid anhydride hydrolase
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UniProt ID | ||||||
EC Number |
EC 3.6.1.5
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Sequence |
MEDTKESNVKTFCSKNILAILGFSSIIAVIALLAVGLTQNKALPENVKYGIVLDAGSSHT
SLYIYKWPAEKENDTGVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQ HQETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARIITGQEEGAYGWI TINYLLGKFSQKTRWFSIVPYETNNQETFGALDLGGASTQVTFVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTP CTKRFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPLQGDFGAF SAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWEEIKTSYAGVKEKYLSEYCFSGTYIL SLLLQGYHFTADSWEHIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHSTYVFL MVLFSLVLFTVAIIGLLIFHKPSYFWKDMV Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
1 | IPH5201 | Drug Info | Phase 1 | Solid tumour/cancer | [2] | |
2 | SRF617 | Drug Info | Phase 1 | Solid tumour/cancer | [3] | |
3 | TTX-030 | Drug Info | Phase 1 | Lymphoma | [4] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 4 Inhibitor drugs | + | ||||
1 | IPH5201 | Drug Info | [2] | |||
2 | TTX-030 | Drug Info | [6] | |||
3 | PSB-0963 | Drug Info | [7] | |||
4 | PSB-6426 | Drug Info | [1] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Purine metabolism | hsa00230 | Affiliated Target |
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Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy | ||
Pyrimidine metabolism | hsa00240 | Affiliated Target |
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Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy |
Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 1.32E-04 |
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Closeness centrality | 1.50E-01 | Radiality | 1.20E+01 | Clustering coefficient | 1.67E-01 |
Neighborhood connectivity | 7.25E+00 | Topological coefficient | 3.38E-01 | Eccentricity | 14 |
Download | Click to Download the Full PPI Network of This Target | ||||
Chemical Structure based Activity Landscape of Target | Top |
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Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Affiliated Biological Pathways | Top | |||||
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BioCyc | [+] 1 BioCyc Pathways | + | ||||
1 | UTP and CTP dephosphorylation II | |||||
KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
1 | Purine metabolism | |||||
2 | Pyrimidine metabolism | |||||
3 | Epstein-Barr virus infection |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Selective nucleoside triphosphate diphosphohydrolase-2 (NTPDase2) inhibitors: nucleotide mimetics derived from uridine-5'-carboxamide. J Med Chem. 2008 Aug 14;51(15):4518-28. | |||||
REF 2 | ClinicalTrials.gov (NCT04261075) IPH5201 as Monotherapy or in Combination With Durvalumab +/- Oleclumab in Subjects With Advanced Solid Tumors.. U.S. National Institutes of Health. | |||||
REF 3 | ClinicalTrials.gov (NCT04336098) Study of SRF617 in Patients With Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
REF 4 | ClinicalTrials.gov (NCT03884556) TTX-030 Single Agent and in Combination With Immunotherapy or Chemotherapy for Patients With Advanced Cancers. U.S. National Institutes of Health. | |||||
REF 5 | Clinical pipeline report, company report or official report of Surface oncology. | |||||
REF 6 | Clinical pipeline report, company report or official report of AbbVie. | |||||
REF 7 | Development of potent and selective inhibitors of ecto-5'-nucleotidase based on an anthraquinone scaffold. J Med Chem. 2010 Mar 11;53(5):2076-86. |
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