Target Information

Target General Infomation
Target ID
T03661 (Former ID: TTDS00092)
Target Name
Adenosine deaminase (ADA)
Synonyms
Adenosine aminohydrolase; ADA1
Gene Name
ADA
Target Type
Successful target
 [1]
Disease [+] 3 Target-related Diseases +
1 Adaptive immunity immunodeficiency [ICD-11: 4A01]
2 Malignant haematopoietic neoplasm [ICD-11: 2B33]
3 Mature B-cell leukaemia [ICD-11: 2A82]
Function
Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4. Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion. Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion. Enhances CD4+ T-cell differentiation and proliferation. Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change. Stimulates plasminogen activation. Plays a role in male fertility. Plays a protective role in early postimplantation embryonic development. Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine.
BioChemical Class
Carbon-nitrogen hydrolase
UniProt ID
ADA_HUMAN
EC Number
EC 3.5.4.4
Sequence
MAQTPAFDKPKVELHVHLDGSIKPETILYYGRRRGIALPANTAEGLLNVIGMDKPLTLPD
FLAKFDYYMPAIAGCREAIKRIAYEFVEMKAKEGVVYVEVRYSPHLLANSKVEPIPWNQA
EGDLTPDEVVALVGQGLQEGERDFGVKARSILCCMRHQPNWSPKVVELCKKYQQQTVVAI
DLAGDETIPGSSLLPGHVQAYQEAVKSGIHRTVHAGEVGSAEVVKEAVDILKTERLGHGY
HTLEDQALYNRLRQENMHFEICPWSSYLTGAWKPDTEHAVIRLKNDQANYSLNTDDPLIF
KSTLDTDYQMTKRDMGFTEEEFKRLNINAAKSSFLPEDEKRELLDLLYKAYGMPPSASAG
QNL
Drugs and Modes of Action
Approved Drug(s) [+] 4 Approved Drugs +
1 Cladribine Drug Info Approved Hairy cell leukaemia [2], [3]
2 Elapegademase Drug Info Approved Adenosine deaminase defciency [4]
3 Fludarabine Drug Info Approved Haematological malignancy [5], [6]
4 Pentostatin Drug Info Approved Hairy cell leukaemia [6], [7]
Clinical Trial Drug(s) [+] 3 Clinical Trial Drugs +
1 GSK2696273 Drug Info Preregistration Chronic pain [8]
2 EZN-2279 Drug Info Phase 3 Immunodeficiency [9]
3 Ex vivo adenosine deaminase-transduced hematopoietic stem cell therapy Drug Info Phase 1/2 Immunodeficiency [10]
Mode of Action [+] 2 Modes of Action +
Inhibitor [+] 25 Inhibitor drugs +
1 Cladribine Drug Info [1], [11]
2 Fludarabine Drug Info [12]
3 Pentostatin Drug Info [12], [13]
4 (2S,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-ol Drug Info [16]
5 1-Deaza-Adenosine Drug Info [17]
6 3-(6-Amino-purin-9-yl)-4-butoxy-butan-2-ol Drug Info [18]
7 3-(6-Amino-purin-9-yl)-4-p-tolyl-butan-2-ol Drug Info [18]
8 3-(6-Amino-purin-9-yl)-4-phenethyloxy-butan-2-ol Drug Info [18]
9 3-(6-Amino-purin-9-yl)-5-m-tolyl-pentan-2-ol Drug Info [18]
10 3-(6-Amino-purin-9-yl)-6-o-tolyl-hexan-2-ol Drug Info [18]
11 3-(6-Amino-purin-9-yl)-6-phenyl-hexan-2-ol Drug Info [18]
12 3-(6-Amino-purin-9-yl)-7-phenyl-heptan-2-ol Drug Info [18]
13 3-(6-Amino-purin-9-yl)-8-phenyl-octan-2-ol Drug Info [18]
14 3-(6-Amino-purin-9-yl)-non-5-en-2-ol Drug Info [18]
15 3-(6-Amino-purin-9-yl)-non-5-yn-2-ol Drug Info [18]
16 6-Hydroxy-1,6-Dihydro Purine Nucleoside Drug Info [17]
17 6-Hydroxy-7,8-Dihydro Purine Nucleoside Drug Info [17]
18 EHNA Drug Info [19]
19 FR117016 Drug Info [16]
20 FR221647 Drug Info [16]
21 FR230513 Drug Info [16]
22 FR233623 Drug Info [16]
23 FR236913 Drug Info [16]
24 FR239087 Drug Info [16]
25 Purine Riboside Drug Info [17]
Modulator [+] 4 Modulator drugs +
1 Elapegademase Drug Info [4]
2 GSK2696273 Drug Info [14]
3 EZN-2279 Drug Info [15]
4 Ex vivo adenosine deaminase-transduced hematopoietic stem cell therapy Drug Info [14]
Target Regulators
Target-regulating microRNAs
Target-regulating microRNAs Info 
Target-regulating Transcription Factors
Target-regulating Transcription Factors Info 
Target Affiliated Biological Pathways
BioCyc [+] 6 BioCyc Pathways +
1 Purine nucleotides degradation
2 Purine deoxyribonucleosides degradation
3 Purine ribonucleosides degradation to ribose-1-phosphate
4 Adenosine nucleotides degradation
5 Superpathway of purine nucleotide salvage
6 Adenine and adenosine salvage III
KEGG Pathway [+] 3 KEGG Pathways +
1 Purine metabolism
2 Metabolic pathways
3 Primary immunodeficiency
NetPath Pathway [+] 2 NetPath Pathways +
1 TCR Signaling Pathway
2 IL2 Signaling Pathway
Panther Pathway [+] 1 Panther Pathways +
1 Adenine and hypoxanthine salvage pathway
Pathwhiz Pathway [+] 1 Pathwhiz Pathways +
1 Purine Metabolism
PID Pathway [+] 4 PID Pathways +
1 p73 transcription factor network
2 C-MYB transcription factor network
3 Validated transcriptional targets of deltaNp63 isoforms
4 Validated transcriptional targets of TAp63 isoforms
Reactome [+] 1 Reactome Pathways +
1 Purine salvage
WikiPathways [+] 1 WikiPathways +
1 Metabolism of nucleotides
Target-Related Models and Studies
Target Validation
Target Validation Info 
References
REF 1 Cladribine: from the bench to the bedside--focus on hairy cell leukemia. Expert Rev Anticancer Ther. 2004 Oct;4(5):745-57.
REF 2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4799).
REF 3 Multiple sclerosis: current and future treatment options. Endocr Metab Immune Disord Drug Targets. 2007 Dec;7(4):292-9.
REF 4 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
REF 5 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4802).
REF 6 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
REF 7 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4805).
REF 8 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033647)
REF 9 ClinicalTrials.gov (NCT01420627) EZN-2279 in Patients With ADA-SCID. U.S. National Institutes of Health.
REF 10 Clinical pipeline report, company report or official report of GlaxoSmithKline.
REF 11 Cladribine. Ortho Biotech Inc. Curr Opin Investig Drugs. 2001 Dec;2(12):1751-6.
REF 12 Purine nucleoside analogs in indolent non-Hodgkin's lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5.
REF 13 Acquisition of resistance to anticancer agents by overproduction of target enzymes. Nippon Rinsho. 1997 May;55(5):1030-7.
REF 14 Clinical pipeline report, company report or official report of GlaxoSmithKline.
REF 15 Clinical pipeline report, company report or official report of Sigma-Tau Pharmaceuticals, Inc.
REF 16 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
REF 17 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
REF 18 Adenosine deaminase inhibitors: synthesis and biological evaluation of unsaturated, aromatic, and oxo derivatives of (+)-erythro-9-(2'S-hydroxy-3'R... J Med Chem. 2000 Nov 30;43(24):4694-700.
REF 19 Tight-binding inhibitors--IV. Inhibition of adenosine deaminases by various inhibitors. Biochem Pharmacol. 1977 Mar 1;26(5):359-67.

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