Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTK0O6Y)

• DTT Name: Ecto-5'-nucleotidase (CD73)
• Synonyms: NT5; CD73 antigen; 5'-nucleotidase; 5'-NT
• Gene Name: NT5E
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Phosphoric monoester hydrolase
• UniProt ID: 5NTD_HUMAN
• TTD ID: T65116
• EC Number: EC 3.1.3.5
• Sequence:
  MCPRAARAPATLLLALGAVLWPAAGAWELTILHTNDVHSRLEQTSEDSSKCVNASRCMGG
  VARLFTKVQQIRRAEPNVLLLDAGDQYQGTIWFTVYKGAEVAHFMNALRYDAMALGNHEF
  DNGVEGLIEPLLKEAKFPILSANIKAKGPLASQISGLYLPYKVLPVGDEVVGIVGYTSKE
  TPFLSNPGTNLVFEDEITALQPEVDKLKTLNVNKIIALGHSGFEMDKLIAQKVRGVDVVV
  GGHSNTFLYTGNPPSKEVPAGKYPFIVTSDDGRKVPVVQAYAFGKYLGYLKIEFDERGNV
  ISSHGNPILLNSSIPEDPSIKADINKWRIKLDNYSTQELGKTIVYLDGSSQSCRFRECNM
  GNLICDAMINNNLRHTDEMFWNHVSMCILNGGGIRSPIDERNNGTITWENLAAVLPFGGT
  FDLVQLKGSTLKKAFEHSVHRYGQSTGEFLQVGGIHVVYDLSRKPGDRVVKLDVLCTKCR
  VPSYDPLKMDEVYKVILPNFLANGGDGFQMIKDELLRHDSGDQDINVVSTYISKMKVIYP
  AVEGRIKFSTGSHCHGSFSLIFLSLWAVIFVLYQ
• Function: Exhibits AMP-, NAD-, and NMN-nucleosidase activities. Hydrolyzes extracellular nucleotides into membrane permeable nucleosides.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Pyrimidine metabolism (hsa00240)
  Nicotinate and nicotinamide metabolism (hsa00760)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Purine catabolism (R-HSA-74259)
• BioCyc Pathway: MetaCyc:HS05981-MON

Molecular Interaction Atlas (MIA) of This DTT

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	[2]
AB680	DMGONUE	Pancreatic cancer	2C10	Phase 1	[3]
CPI-006	DMJSFTX	Advanced cancer	2A00-2F9Z	Phase 1	[4]
GS-1423	DMS25DL	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
LY3475070	DMZLIWX	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
NZV930	DMWN2FP	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
Oleclumab	DMLVNWO	Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]
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]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Prostate cancer	2C82	Prostate	9.56E-01	0.33	0.37

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Ecto-5'-nucleotidase (NT5E) DME Info
• Gene Name: NT5E

1 Approved Drug(s) Metabolized by This DTT

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

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] 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.
• [3] Discovery of AB680: A Potent and Selective Inhibitor of CD73. J Med Chem. 2020 Oct 22;63(20):11448-11468.
• [4] Clinical pipeline report, company report or official report of Corvus Pharmaceuticals.
• [5] Clinical pipeline report, company report or official report of Agenus.
• [6] CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers. Front Immunol. 2020 Apr 15;11:508.
• [7] Clinical pipeline report, company report or official report of Surface oncology.
• [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.