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 | |||||
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 Transcription Factors | |||||
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 | |||||
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. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Wang and Dr. Li.