Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DE3Z9HM)

• DME Name: Ecto-5'-nucleotidase (NT5E)
• Synonyms: Ecto-nucleotidase; 5'-NT; 5'-nucleotidase; Ectonucleotidase; CD73; NT5; NT5E; NTE
• Gene Name: NT5E
• UniProt ID: 5NTD_HUMAN
• INTEDE ID: DME0111
• Gene ID: 4907
• EC Number:
  EC: 3.1.3.5
  Hydrolases
  Ester bond hydrolase
  Phosphoric monoester hydrolase
  EC: 3.1.3.5
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MCPRAARAPATLLLALGAVLWPAAGAWELTILHTNDVHSRLEQTSEDSSKCVNASRCMGG
  VARLFTKVQQIRRAEPNVLLLDAGDQYQGTIWFTVYKGAEVAHFMNALRYDAMALGNHEF
  DNGVEGLIEPLLKEAKFPILSANIKAKGPLASQISGLYLPYKVLPVGDEVVGIVGYTSKE
  TPFLSNPGTNLVFEDEITALQPEVDKLKTLNVNKIIALGHSGFEMDKLIAQKVRGVDVVV
  GGHSNTFLYTGNPPSKEVPAGKYPFIVTSDDGRKVPVVQAYAFGKYLGYLKIEFDERGNV
  ISSHGNPILLNSSIPEDPSIKADINKWRIKLDNYSTQELGKTIVYLDGSSQSCRFRECNM
  GNLICDAMINNNLRHTDEMFWNHVSMCILNGGGIRSPIDERNNGTITWENLAAVLPFGGT
  FDLVQLKGSTLKKAFEHSVHRYGQSTGEFLQVGGIHVVYDLSRKPGDRVVKLDVLCTKCR
  VPSYDPLKMDEVYKVILPNFLANGGDGFQMIKDELLRHDSGDQDINVVSTYISKMKVIYP
  AVEGRIKFSTGSHCHGSFSLIFLSLWAVIFVLYQ
• Function: This enzyme hydrolyzes extracellular nucleotides into membrane permeable nucleosides and exhibits AMP-, NAD-, and NMN-nucleosidase activities.
• KEGG Pathway:
  Metabolic pathways (hsa01100)
  Nicotinate and nicotinamide metabolism (hsa00760)
  Purine metabolism (hsa00230)
  Pyrimidine metabolism (hsa00240)
• Reactome Pathway:
  Purine catabolism (R-HSA-74259)
  Pyrimidine catabolism (R-HSA-73621)
  Nicotinate metabolism (R-HSA-196807)

Molecular Interaction Atlas (MIA) of This DME

1 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cytarabine	DMZD5QR	Acute lymphoblastic leukaemia	2A85	Approved	[13]

Molecular Expression Atlas (MEA) of This DME

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	7.37E-02	-1.10E-01	-5.68E-01
Alopecia	ED70	Skin from scalp	3.01E-04	2.15E-01	6.13E-01
Alzheimer's disease	8A20	Entorhinal cortex	4.79E-04	-1.61E-01	-4.77E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	5.33E-01	2.65E-02	1.23E-01
Aortic stenosis	BB70	Calcified aortic valve	7.20E-01	3.94E-01	3.61E-01
Apnea	7A40	Hyperplastic tonsil	2.81E-01	6.27E-01	1.82E+00
Arthropathy	FA00-FA5Z	Peripheral blood	5.15E-01	-1.34E-01	-3.59E-01
Asthma	CA23	Nasal and bronchial airway	2.19E-01	6.68E-03	1.31E-02
Atopic dermatitis	EA80	Skin	4.25E-05	-4.68E-01	-7.77E-01
Autism	6A02	Whole blood	3.68E-01	-1.40E-01	-4.42E-01
Autoimmune uveitis	9A96	Peripheral monocyte	4.40E-02	-1.71E-01	-3.05E+00
Autosomal dominant monocytopenia	4B04	Whole blood	3.20E-03	-2.05E-01	-1.24E+00
Bacterial infection of gingival	1C1H	Gingival tissue	4.50E-12	3.93E-01	1.38E+00
Batten disease	5C56.1	Whole blood	9.30E-01	-2.32E-01	-3.85E-01
Behcet's disease	4A62	Peripheral blood	3.53E-01	-2.49E-01	-5.96E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	8.45E-01	8.21E-02	2.77E-01
Bladder cancer	2C94	Bladder tissue	9.86E-02	-7.93E-01	-1.07E+00
Breast cancer	2C60-2C6Z	Breast tissue	4.64E-51	-9.07E-01	-1.39E+00
Cardioembolic stroke	8B11.20	Whole blood	2.74E-05	-7.57E-01	-1.37E+00
Cervical cancer	2C77	Cervical tissue	9.97E-01	-1.15E-01	-1.70E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	1.41E-01	2.84E-01	4.47E-01
Chronic hepatitis C	1E51.1	Whole blood	9.83E-01	-7.43E-02	-1.34E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	2.90E-01	-1.01E-01	-3.56E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	1.89E-08	-3.41E-01	-8.67E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	9.88E-01	3.14E-02	6.65E-02
Colon cancer	2B90	Colon tissue	2.15E-03	9.95E-02	2.00E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	9.93E-02	-2.50E-01	-1.02E+00
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	4.58E-01	1.01E-01	3.72E-01
Endometriosis	GA10	Endometrium tissue	4.13E-01	4.38E-01	3.16E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	4.19E-02	2.21E-01	4.67E-01
Familial hypercholesterolemia	5C80.00	Whole blood	1.55E-12	-5.83E-01	-1.86E+00
Gastric cancer	2B72	Gastric tissue	1.94E-01	1.00E+00	1.40E+00
Glioblastopma	2A00.00	Nervous tissue	1.43E-10	2.44E-01	4.72E-01
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	2.46E-01	7.85E-01	1.38E+00
Glioma	2A00.0Y-2A00.0Z	White matter tissue	6.09E-05	1.14E+00	1.47E+00
Head and neck cancer	2D42	Head and neck tissue	5.90E-04	1.79E-01	4.17E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	1.06E-01	-1.93E-01	-6.17E-01
Huntington's disease	8A01.10	Whole blood	1.57E-01	-1.67E-01	-7.22E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	1.48E-02	4.30E-01	1.74E+00
Immunodeficiency	4A00-4A20	Peripheral blood	7.83E-02	-6.12E-01	-1.01E+00
Influenza	1E30	Whole blood	6.61E-01	-5.83E-01	-5.64E-01
Interstitial cystitis	GC00.3	Bladder tissue	3.10E-01	-1.27E-01	-3.94E-01
Intracranial aneurysm	8B01.0	Intracranial artery	4.93E-01	-4.62E-01	-9.10E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	8.53E-01	4.87E-02	1.56E-01
Ischemic stroke	8B11	Peripheral blood	7.30E-01	9.01E-02	2.65E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	1.02E-02	-1.78E-01	-3.30E-01
Lateral sclerosis	8B60.4	Skin	5.93E-01	1.66E-01	3.99E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	6.82E-01	-3.67E-02	-9.03E-02
Liver cancer	2C12.0	Liver tissue	6.09E-19	-7.88E-01	-2.34E+00
Liver failure	DB99.7-DB99.8	Liver tissue	9.01E-04	-9.85E-01	-3.32E+00
Lung cancer	2C25	Lung tissue	1.97E-39	5.96E-01	1.46E+00
Lupus erythematosus	4A40	Whole blood	1.80E-02	-6.30E-02	-8.70E-02
Major depressive disorder	6A70-6A7Z	Hippocampus	3.01E-01	-9.17E-02	-3.18E-01
Major depressive disorder	6A70-6A7Z	Whole blood	5.10E-01	-1.15E-02	-2.90E-02
Melanoma	2C30	Skin	4.52E-01	1.25E-01	7.38E-02
Multiple myeloma	2A83.1	Peripheral blood	3.96E-01	1.03E-01	4.33E-01
Multiple myeloma	2A83.1	Bone marrow	4.25E-02	-3.03E-01	-2.76E+00
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	1.84E-01	2.31E-01	6.87E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	3.50E-01	4.70E-02	1.75E-01
Myelofibrosis	2A20.2	Whole blood	3.19E-04	-3.55E-01	-1.60E+00
Myocardial infarction	BA41-BA50	Peripheral blood	2.09E-04	-3.61E-01	-4.72E-01
Myopathy	8C70.6	Muscle tissue	1.43E-02	1.98E-01	1.03E+00
Neonatal sepsis	KA60	Whole blood	8.16E-17	-5.37E-01	-1.25E+00
Neuroectodermal tumour	2A00.11	Brain stem tissue	5.75E-04	-5.96E-01	-1.71E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	7.88E-02	-4.56E-01	-1.44E+00
Obesity related type 2 diabetes	5A11	Omental adipose tissue	9.70E-01	-1.38E-01	-3.22E-01
Olive pollen allergy	CA08.00	Peripheral blood	3.33E-01	-2.96E-01	-3.83E-01
Oral cancer	2B6E	Oral tissue	4.23E-15	1.14E+00	2.45E+00
Osteoarthritis	FA00-FA0Z	Synovial tissue	1.25E-01	8.66E-01	5.91E-01
Osteoporosis	FB83.1	Bone marrow	1.12E-01	-4.50E-01	-1.57E+00
Ovarian cancer	2C73	Ovarian tissue	4.45E-03	-1.68E+00	-2.08E+00
Pancreatic cancer	2C10	Pancreas	1.02E-07	9.73E-01	2.01E+00
Parkinson's disease	8A00.0	Substantia nigra tissue	3.18E-01	-1.95E-01	-9.82E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	1.08E-02	-4.97E-01	-8.84E-01
Pituitary cancer	2D12	Pituitary tissue	1.01E-01	5.78E-01	1.00E+00
Pituitary gonadotrope tumour	2D12	Pituitary tissue	7.48E-01	6.17E-01	9.56E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	1.51E-02	-1.26E-01	-1.37E+00
Polycythemia vera	2A20.4	Whole blood	6.40E-03	-1.32E-01	-6.15E-01
Pompe disease	5C51.3	Biceps muscle	2.29E-01	-2.40E-01	-1.04E+00
Preterm birth	KA21.4Z	Myometrium	2.12E-01	3.10E-01	7.85E-01
Prostate cancer	2C82	Prostate	9.56E-01	3.25E-01	3.67E-01
Psoriasis	EA90	Skin	7.16E-09	-3.53E-01	-6.21E-01
Rectal cancer	2B92	Rectal colon tissue	1.95E-01	-2.16E-01	-6.77E-01
Renal cancer	2C90-2C91	Kidney	3.64E-02	4.69E-01	6.06E-01
Retinoblastoma	2D02.2	Uvea	8.66E-07	-2.96E+00	-4.66E+00
Rheumatoid arthritis	FA20	Synovial tissue	1.81E-02	7.18E-01	1.08E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	6.14E-01	-1.34E-01	-4.82E-01
Schizophrenia	6A20	Prefrontal cortex	1.55E-01	5.81E-02	1.65E-01
Schizophrenia	6A20	Superior temporal cortex	1.36E-01	-1.03E-01	-7.14E-01
Scleroderma	4A42.Z	Whole blood	8.50E-02	-1.84E-01	-6.33E-01
Seizure	8A60-8A6Z	Whole blood	8.06E-01	6.78E-02	1.03E-01
Sensitive skin	EK0Z	Skin	4.15E-01	-1.76E-01	-8.69E-01
Sepsis with septic shock	1G41	Whole blood	3.37E-50	-7.39E-01	-1.75E+00
Shwachman-Diamond syndrome	3A70.0	Bone marrow	2.76E-01	-1.29E-01	-3.52E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	1.75E-03	-4.14E-01	-1.29E+00
Simpson golabi behmel syndrome	LD2C	Adipose tissue	2.71E-02	4.32E-01	3.35E+00
Sjogren's syndrome	4A43.2	Salivary gland tissue	4.82E-01	1.60E-01	5.11E-01
Skin cancer	2C30-2C3Z	Skin	1.32E-01	-3.49E-01	-5.93E-01
Thrombocythemia	3B63	Whole blood	4.14E-01	7.33E-02	3.35E-01
Thrombocytopenia	3B64	Whole blood	3.96E-02	-3.58E-01	-5.59E-01
Thyroid cancer	2D10	Thyroid	9.12E-25	1.03E+00	1.76E+00
Tibial muscular dystrophy	8C75	Muscle tissue	1.87E-08	1.25E+00	5.33E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	3.62E-01	-1.85E-01	-1.43E+00
Type 2 diabetes	5A11	Liver tissue	3.92E-02	4.14E-01	1.20E+00
Ureter cancer	2C92	Urothelium	8.10E-01	-5.33E-02	-3.74E-01
Uterine cancer	2C78	Endometrium tissue	1.60E-10	-9.80E-01	-1.01E+00
Vitiligo	ED63.0	Skin	6.48E-01	3.96E-01	8.57E-01

The Drug Therapeutic Target (DTT) Role of This DME

• DME DTT Name: Ecto-5'-nucleotidase (CD73) DTT Info
• DME DTT Type: Clinical trial

8 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TJ004309	DMFB54Y	Ovarian cancer	2C73	Phase 2	[1]
AB680	DMGONUE	Pancreatic cancer	2C10	Phase 1	[2]
CPI-006	DMJSFTX	Advanced cancer	2A00-2F9Z	Phase 1	[3]
GS-1423	DMS25DL	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
LY3475070	DMZLIWX	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
NZV930	DMWN2FP	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
Oleclumab	DMLVNWO	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
TJ4309	DMM3U2Q	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]

34 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID28870136-Compound-36	DMQJF15	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-37	DMAPMG2	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-38	DM67XSL	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-39	DMU18W6	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-40	DMJP0AG	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-41	DMSWM9Q	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-42	DMV0R2X	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-43	DMWGV8N	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-44	DMNOAQB	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-45	DM1QHV0	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-46	DM4FD7C	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-47	DMYWBRX	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-48	DMPIM9L	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-49	DMTUC9E	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-50	DM42OYU	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-51	DMU3MQB	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-52	DMFDERP	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-53	DMLEWY6	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-54	DM6HOES	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-55	DMVRJZX	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-56	DMK0RTV	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-57	DME3HLC	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-58	DMQIUD9	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-59	DMHP90Q	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-60	DM39QU8	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-61	DMFNU9D	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-62	DMNKXJ2	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-63	DM26WNY	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-64	DMBKSVH	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-65	DMF5K9J	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-67	DME3YRI	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-68	DMFTM8X	N. A.	N. A.	Patented	[9]
PMID28870136-Compound-69	DMVCQKB	N. A.	N. A.	Patented	[9]
PMID29166791-Compound-AMPCP	DMDN4KP	N. A.	N. A.	Patented	[10]

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acid blue 25	DMCU6XV	Discovery agent	N.A.	Investigative	[11]
alphabeta-methyleneADP	DMRGFEM	Discovery agent	N.A.	Investigative	[12]
PSB-0952	DMW19LB	Discovery agent	N.A.	Investigative	[11]
PSB-0963	DMBDVJ1	Discovery agent	N.A.	Investigative	[11]
RB 2	DMCEFUW	Discovery agent	N.A.	Investigative	[11]

References

• [1] ClinicalTrials.gov (NCT05001347) A Phase 2 Clinical Study of TJ004309 in Combination With Atezolizumab (TECENTRIQ?) in Patients With Advanced or Metastatic Ovarian Cancers and Selected Advanced Solid Tumors. U.S.National Institutes of Health.
• [2] Discovery of AB680: A Potent and Selective Inhibitor of CD73. J Med Chem. 2020 Oct 22;63(20):11448-11468.
• [3] Clinical pipeline report, company report or official report of Corvus Pharmaceuticals.
• [4] Clinical pipeline report, company report or official report of Agenus.
• [5] CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers. Front Immunol. 2020 Apr 15;11:508.
• [6] Clinical pipeline report, company report or official report of Surface oncology.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] ClinicalTrials.gov (NCT04322006) A Phase I/II Study of TJ004309 for Advanced Solid Tumor. U.S. National Institutes of Health.
• [9] Ectonucleotidase inhibitors: a patent review (2011-2016).Expert Opin Ther Pat. 2017 Dec;27(12):1291-1304.
• [10] Evaluation of WO2017098421: GSK's benzothiazine compounds as CD73 inhibitor filings.Expert Opin Ther Pat. 2018 Feb;28(2):167-171.
• [11] 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.
• [12] 5'-Nucleotidase from smooth muscle of small intestine and from brain. Inhibition of nucleotides. Biochemistry. 1975 Jun 3;14(11):2362-6.
• [13] Genetic factors influencing cytarabine therapy. Pharmacogenomics. 2009 Oct;10(10):1657-74.