Top ▲
target has curated data in GtoImmuPdb
Target id: 1232
Nomenclature: Ecto-5'-Nucleotidase
Abbreviated Name: NT5E
Systematic Nomenclature: CD73
Family: Adenosine turnover
Gene and Protein Information  |
||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 574 | 6q14.3 | NT5E | 5'-nucleotidase ecto | |
| Mouse | - | 576 | 9 E3.1 | Nt5e | 5' nucleotidase, ecto | |
| Rat | - | 576 | 8q31 | Nt5e | 5' nucleotidase, ecto | |
| Previous and Unofficial Names |
| 5' nucleotidase, ecto | 5' nucleotidase | 5' nucleotidase (CD73) | 5' nucleotidase, ecto | 5'-nucleotidase, ecto (CD73) | ecto-5'-nucleotidase | eN | eNT | NT5 |
| Database Links |
|
| Alphafold | P21589 (Hs), Q61503 (Mm), P21588 (Rn) |
| BRENDA | 3.1.3.5 |
| CATH/Gene3D | 3.60.21.10, 3.90.780.10 |
| ChEMBL Target | CHEMBL5957 (Hs), CHEMBL4680034 (Mm), CHEMBL1075214 (Rn) |
| Ensembl Gene | ENSG00000135318 (Hs), ENSMUSG00000032420 (Mm), ENSRNOG00000011071 (Rn) |
| Entrez Gene | 4907 (Hs), 23959 (Mm), 58813 (Rn) |
| Human Protein Atlas | ENSG00000135318 (Hs) |
| KEGG Enzyme | 3.1.3.5 |
| KEGG Gene | hsa:4907 (Hs), mmu:23959 (Mm), rno:58813 (Rn) |
| OMIM | 129190 (Hs) |
| Pharos | P21589 (Hs) |
| SynPHARM | 13827 (in complex with αβ-methyleneADP) |
| UniProtKB | P21589 (Hs), Q61503 (Mm), P21588 (Rn) |
| Wikipedia | NT5E (Hs) |
| Enzyme Reaction |
||||
|
||||
| Rank order of affinity (Human) |
| adenosine 5'-monophosphate, 5'-GMP, 5'-inosine monophosphate, 5'-UMP > 5'-dAMP, 5'-dGMP |
Download all structure-activity data for this target as a CSV file 
| Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| View species-specific inhibitor tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antibodies | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Immunopharmacology Comments |
| Via the conversion of ADP/ATP to AMP (CD39; ENTPD1) and AMP to adenosine (CD73; NT5E) these ectonucleotidase enzymes are crucial to the regulation of purinergic signals delivered to immune cells [1]. Increased adenosine levels are reported in tumours, and drives a shift to an anti-inflammatory environment which can promote tumour growth [17]. Increasing evidence validates both of these enzymes as potential druggable targets in cancer [3,9,15]. CD73 is immunosuppressive and pro-metastatic. CD73 on tumour cells, increases extracellular adenosine levels which inhibits the function of tumour-reactive CD8+ cells via A2A adenosine receptors, and enhances tumour cell invasion and chemotaxis (the latter via A2B adenosine receptors) [15]. Anti-CD73 mAbs that target this adenosine-driven immunosuppressive pathway are being exploited for their potential to re-activate anti-tumour immune responses across a wide range of tumours. Bristol-Myers Squibb, MedImmune and Innate Pharma (preclinical) have ongoing anti-CD73 immuno-oncology programmes (September 2017). Examples of clinical evaluations of anti-CD73 mAbs in patients with advanced solid tumours: MedImmune's oleclumab (MEDI9447) is being evaluated alone and in combination with anti PD-L1 mAb durvalumab (MEDI4736) in Phase 1 clinical trial NCT02503774. Bristol-Myers' BMS-986179 is being tested in combination with the anti-PD-1 mAb nivolumab (BMS-936558) in Phase 1/2 trial NCT02754141. |
| Immuno Process Associations | ||
|
||
|
||
|
| General Comments |
| CD73 is membrane-bound extracellular enzyme that, together with CD39, plays a major role in promoting immunosuppression through the pathway that degrades adenosine triphosphate (ATP) into adenosine. CD73 performs the terminal catalytic step in conversion to adenosine. It is overexpressed in several cancer types, and this has been linked with poor prognosis in certain cancers [10,12-14,16,19]. Adenosine accumulation driven by this pathway in the tumour microenvironment causes immune suppression, is pro-angiogenic and stimulates tumour metastasis. |
1. Antonioli L, Pacher P, Vizi ES, Haskó G. (2013) CD39 and CD73 in immunity and inflammation. Trends Mol Med, 19 (6): 355-67. [PMID:23601906]
2. Baqi Y, Lee SY, Iqbal J, Ripphausen P, Lehr A, Scheiff AB, Zimmermann H, Bajorath J, Müller CE. (2010) Development of potent and selective inhibitors of ecto-5'-nucleotidase based on an anthraquinone scaffold. J Med Chem, 53 (5): 2076-86. [PMID:20146483]
3. Bastid J, Cottalorda-Regairaz A, Alberici G, Bonnefoy N, Eliaou JF, Bensussan A. (2013) ENTPD1/CD39 is a promising therapeutic target in oncology. Oncogene, 32 (14): 1743-51. [PMID:22751118]
4. Bhattarai S, Pippel J, Scaletti E, Idris R, Freundlieb M, Rolshoven G, Renn C, Lee SY, Abdelrahman A, Zimmermann H et al.. (2020) 2-Substituted α,β-Methylene-ADP Derivatives: Potent Competitive Ecto-5'-nucleotidase (CD73) Inhibitors with Variable Binding Modes. J Med Chem, 63 (6): 2941-2957. [PMID:32045236]
5. Bowman CE, da Silva RG, Pham A, Young SW. (2019) An Exceptionally Potent Inhibitor of Human CD73. Biochemistry, 58 (31): 3331-3334. [PMID:31334635]
6. Du X, Eksterowicz J, Fantin VR, Sun D, Ye Q, Moore J, Zavorotinskaya T, Blank BR, Rew Y, Wu K et al.. (2021) Cd73 inhibitors. Patent number: WO2021087136A1. Assignee: Oric Pharmaceuticals, Inc.. Priority date: 29/10/2020. Publication date: 06/05/2021.
7. Geoghegan JC, Diedrich G, Lu X, Rosenthal K, Sachsenmeier KF, Wu H, Dall'Acqua WF, Damschroder MM. (2016) Inhibition of CD73 AMP hydrolysis by a therapeutic antibody with a dual, non-competitive mechanism of action. MAbs, 8 (3): 454-67. [PMID:26854859]
8. Griffin EP, Miller RA, Frey GJ, Chang HW. (2017) Humanized anti-cd73 antibodies. Patent number: WO2017100670A1. Assignee: Corvus Pharmaceuticals. Priority date: 09/12/2015. Publication date: 15/06/2017.
9. Häusler SF, Del Barrio IM, Diessner J, Stein RG, Strohschein J, Hönig A, Dietl J, Wischhusen J. (2014) Anti-CD39 and anti-CD73 antibodies A1 and 7G2 improve targeted therapy in ovarian cancer by blocking adenosine-dependent immune evasion. Am J Transl Res, 6 (2): 129-39. [PMID:24489992]
10. Leclerc BG, Charlebois R, Chouinard G, Allard B, Pommey S, Saad F, Stagg J. (2016) CD73 Expression Is an Independent Prognostic Factor in Prostate Cancer. Clin Cancer Res, 22 (1): 158-66. [PMID:26253870]
11. Li J, Chen L, Billedeau RJ, Stanton TF, Chiang JTP, Lee CC, Li W, Steggerda S, Emberley E, Gross M et al.. (2023) Discovery of a Series of Potent, Selective, and Orally Bioavailable Nucleoside Inhibitors of CD73 That Demonstrates In Vivo Antitumor Activity. J Med Chem, 66 (1): 345-370. [PMID:36529947]
12. Loi S, Pommey S, Haibe-Kains B, Beavis PA, Darcy PK, Smyth MJ, Stagg J. (2013) CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer. Proc Natl Acad Sci USA, 110 (27): 11091-6. [PMID:23776241]
13. Lu XX, Chen YT, Feng B, Mao XB, Yu B, Chu XY. (2013) Expression and clinical significance of CD73 and hypoxia-inducible factor-1α in gastric carcinoma. World J Gastroenterol, 19 (12): 1912-8. [PMID:23569336]
14. Ren ZH, Lin CZ, Cao W, Yang R, Lu W, Liu ZQ, Chen YM, Yang X, Tian Z, Wang LZ et al.. (2016) CD73 is associated with poor prognosis in HNSCC. Oncotarget, 7 (38): 61690-61702. [PMID:27557512]
15. Stagg J. (2012) The double-edge sword effect of anti-CD73 cancer therapy. Oncoimmunology, 1 (2): 217-218. [PMID:22720247]
16. Wang H, Lee S, Nigro CL, Lattanzio L, Merlano M, Monteverde M, Matin R, Purdie K, Mladkova N, Bergamaschi D et al.. (2012) NT5E (CD73) is epigenetically regulated in malignant melanoma and associated with metastatic site specificity. Br J Cancer, 106 (8): 1446-52. [PMID:22454080]
17. Wang L, Fan J, Thompson LF, Zhang Y, Shin T, Curiel TJ, Zhang B. (2011) CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice. J Clin Invest, 121 (6): 2371-82. [PMID:21537079]
18. Wilson NS, Waight JD, Jennings SM, Ignatovich O, Briend ECP, Morin BM, Schon O, Campbell S. (2019) Anti-cd73 antibodies and methods of use thereof. Patent number: WO2019173692A2. Assignee: Agenus Inc.. Priority date: 09/03/2018. Publication date: 12/09/2019.
19. Wu XR, He XS, Chen YF, Yuan RX, Zeng Y, Lian L, Zou YF, Lan N, Wu XJ, Lan P. (2012) High expression of CD73 as a poor prognostic biomarker in human colorectal cancer. J Surg Oncol, 106 (2): 130-7. [PMID:22287455]
