Target Information

Target General Infomation
Target ID
T03661
Former ID
TTDS00092
Target Name
Adenosine deaminase
Gene Name
ADA
Synonyms
Adenosine aminohydrolase; ADA
Target Type
Successful
Disease Chronic pain [ICD9: 338.2,780; ICD10: R52.1-R52.2, G89]
Hairy cell leukemia [ICD9: 202.4; ICD10: C91.4]
Hematological malignancies [ICD9: 200-209; ICD10: C81-C86]
Immunodeficiency [ICD9: 279.3; ICD10: D84.9]
Function
Catalyzes the hydrolytic deamination of adenosine and 2- deoxyadenosine. 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.
BioChemical Class
Carbon-nitrogen hydrolase
Target Validation
T03661
UniProt ID
P00813
EC Number
EC 3.5.4.4
Sequence
MAQTPAFDKPKVELHVHLDGSIKPETILYYGRRRGIALPANTAEGLLNVIGMDKPLTLPD
FLAKFDYYMPAIAGCREAIKRIAYEFVEMKAKEGVVYVEVRYSPHLLANSKVEPIPWNQA
EGDLTPDEVVALVGQGLQEGERDFGVKARSILCCMRHQPNWSPKVVELCKKYQQQTVVAI
DLAGDETIPGSSLLPGHVQAYQEAVKSGIHRTVHAGEVGSAEVVKEAVDILKTERLGHGY
HTLEDQALYNRLRQENMHFEICPWSSYLTGAWKPDTEHAVIRLKNDQANYSLNTDDPLIF
KSTLDTDYQMTKRDMGFTEEEFKRLNINAAKSSFLPEDEKRELLDLLYKAYGMPPSASAG
QNL
Drugs and Mode of Action
Drug(s) Cladribine Drug Info Approved Hairy cell leukemia [468028], [536604]
Fludarabine Drug Info Approved Hematological malignancies [468033], [536361]
Pentostatin Drug Info Approved Hairy cell leukemia [468036], [536361]
GSK2696273 Drug Info Preregistration Chronic pain [549202]
EZN-2279 Drug Info Phase 3 Immunodeficiency [523593]
Ex vivo adenosine deaminase-transduced hematopoietic stem cell therapy Drug Info Phase 1/2 Immunodeficiency [551929]
Inhibitor (2S,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-ol Drug Info [551374]
1-Deaza-Adenosine Drug Info [551393]
3-(6-Amino-purin-9-yl)-4-butoxy-butan-2-ol Drug Info [525926]
3-(6-Amino-purin-9-yl)-4-p-tolyl-butan-2-ol Drug Info [525926]
3-(6-Amino-purin-9-yl)-4-phenethyloxy-butan-2-ol Drug Info [525926]
3-(6-Amino-purin-9-yl)-5-m-tolyl-pentan-2-ol Drug Info [525926]
3-(6-Amino-purin-9-yl)-6-o-tolyl-hexan-2-ol Drug Info [525926]
3-(6-Amino-purin-9-yl)-6-phenyl-hexan-2-ol Drug Info [525926]
3-(6-Amino-purin-9-yl)-7-phenyl-heptan-2-ol Drug Info [525926]
3-(6-Amino-purin-9-yl)-8-phenyl-octan-2-ol Drug Info [525926]
3-(6-Amino-purin-9-yl)-non-5-en-2-ol Drug Info [525926]
3-(6-Amino-purin-9-yl)-non-5-yn-2-ol Drug Info [525926]
6-Hydroxy-1,6-Dihydro Purine Nucleoside Drug Info [551393]
6-Hydroxy-7,8-Dihydro Purine Nucleoside Drug Info [551393]
Cladribine Drug Info [535395], [536010]
EHNA Drug Info [534055]
Fludarabine Drug Info [535008]
FR117016 Drug Info [551374]
FR221647 Drug Info [551374]
FR230513 Drug Info [551374]
FR233623 Drug Info [551374]
FR236913 Drug Info [551374]
FR239087 Drug Info [551374]
Pentostatin Drug Info [535008], [538032]
Purine Riboside Drug Info [551393]
Modulator Ex vivo adenosine deaminase-transduced hematopoietic stem cell therapy Drug Info [551928]
EZN-2279 Drug Info [551689]
GSK2696273 Drug Info [551928]
Pathways
BioCyc Pathway Purine nucleotides degradation
Purine deoxyribonucleosides degradation
Purine ribonucleosides degradation to ribose-1-phosphate
Adenosine nucleotides degradation
Superpathway of purine nucleotide salvage
Adenine and adenosine salvage III
KEGG Pathway Purine metabolism
Metabolic pathways
Primary immunodeficiency
NetPath Pathway TCR Signaling Pathway
IL2 Signaling Pathway
PANTHER Pathway Adenine and hypoxanthine salvage pathway
Pathway Interaction Database p73 transcription factor network
C-MYB transcription factor network
Validated transcriptional targets of deltaNp63 isoforms
Validated transcriptional targets of TAp63 isoforms
PathWhiz Pathway Purine Metabolism
Reactome Purine salvage
WikiPathways Metabolism of nucleotides
References
Ref 468028(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 468033(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 468036(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 523593ClinicalTrials.gov (NCT01420627) EZN-2279 in Patients With ADA-SCID. U.S. National Institutes of Health.
Ref 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 536604Multiple sclerosis: current and future treatment options. Endocr Metab Immune Disord Drug Targets. 2007 Dec;7(4):292-9.
Ref 549202Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033647)
Ref 551929Clinical pipeline report, company report or official report of GlaxoSmithKline.
Ref 525926J Med Chem. 2000 Nov 30;43(24):4694-700.Adenosine deaminase inhibitors: synthesis and biological evaluation of unsaturated, aromatic, and oxo derivatives of (+)-erythro-9-(2'S-hydroxy-3'R-nonyl)adenine [(+)-EHNA].
Ref 534055Tight-binding inhibitors--IV. Inhibition of adenosine deaminases by various inhibitors. Biochem Pharmacol. 1977 Mar 1;26(5):359-67.
Ref 535008Purine nucleoside analogs in indolent non-Hodgkin's lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5.
Ref 535395Cladribine. Ortho Biotech Inc. Curr Opin Investig Drugs. 2001 Dec;2(12):1751-6.
Ref 536010Cladribine: from the bench to the bedside--focus on hairy cell leukemia. Expert Rev Anticancer Ther. 2004 Oct;4(5):745-57.
Ref 538032Acquisition of resistance to anticancer agents by overproduction of target enzymes. Nippon Rinsho. 1997 May;55(5):1030-7.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 551689Clinical pipeline report, company report or official report of Sigma-Tau Pharmaceuticals, Inc.
Ref 551928Clinical pipeline report, company report or official report of GlaxoSmithKline.

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