Target Information
| Target General Information | Top | |||||
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| Target ID |
T03661
(Former ID: TTDS00092)
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| Target Name |
Adenosine deaminase (ADA)
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| Synonyms |
Adenosine aminohydrolase; ADA1
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| Gene Name |
ADA
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| Target Type |
Successful target
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[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.
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| BioChemical Class |
Carbon-nitrogen hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.5.4.4
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| Sequence |
MAQTPAFDKPKVELHVHLDGSIKPETILYYGRRRGIALPANTAEGLLNVIGMDKPLTLPD
FLAKFDYYMPAIAGCREAIKRIAYEFVEMKAKEGVVYVEVRYSPHLLANSKVEPIPWNQA EGDLTPDEVVALVGQGLQEGERDFGVKARSILCCMRHQPNWSPKVVELCKKYQQQTVVAI DLAGDETIPGSSLLPGHVQAYQEAVKSGIHRTVHAGEVGSAEVVKEAVDILKTERLGHGY HTLEDQALYNRLRQENMHFEICPWSSYLTGAWKPDTEHAVIRLKNDQANYSLNTDDPLIF KSTLDTDYQMTKRDMGFTEEEFKRLNINAAKSSFLPEDEKRELLDLLYKAYGMPPSASAG QNL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| ADReCS ID | BADD_A05955 ; BADD_A06637 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| 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 | OTL-101 | Drug Info | Phase 3 | Severe combined immunodeficiency | [9] | |
| 3 | Ex vivo adenosine deaminase-transduced hematopoietic stem cell therapy | Drug Info | Phase 1/2 | Immunodeficiency | [10] | |
| Mode of Action | [+] 3 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 | [+] 3 Modulator drugs | + | ||||
| 1 | Elapegademase | Drug Info | [4] | |||
| 2 | GSK2696273 | Drug Info | [14] | |||
| 3 | Ex vivo adenosine deaminase-transduced hematopoietic stem cell therapy | Drug Info | [14] | |||
| Replacement | [+] 1 Replacement drugs | + | ||||
| 1 | OTL-101 | Drug Info | [15] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-regulating Transcription Factors | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| 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 | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| 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 (NCT04140539) A Clinical Study to Enable Process Validation of Commercial Grade OTL-101. 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 Orchard Therapeutics. | |||||
| 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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