Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DE7T5VX)

• DME Name: Adenosine kinase (ADK)
• Synonyms: Adenosine 5'-phosphotransferase; Adenosine monophosphate formation enzyme; ADK; AdK; AK
• Gene Name: ADK
• UniProt ID: ADK_HUMAN
• INTEDE ID: DME0448
• Gene ID: 132
• EC Number:
  EC: 2.7.1.20
  Transferase
  Kinase
  Phosphotransferase
  EC: 2.7.1.20
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MAAAEEEPKPKKLKVEAPQALRENILFGMGNPLLDISAVVDKDFLDKYSLKPNDQILAED
  KHKELFDELVKKFKVEYHAGGSTQNSIKVAQWMIQQPHKAATFFGCIGIDKFGEILKRKA
  AEAHVDAHYYEQNEQPTGTCAACITGDNRSLIANLAAANCYKKEKHLDLEKNWMLVEKAR
  VCYIAGFFLTVSPESVLKVAHHASENNRIFTLNLSAPFISQFYKESLMKVMPYVDILFGN
  ETEAATFAREQGFETKDIKEIAKKTQALPKMNSKRQRIVIFTQGRDDTIMATESEVTAFA
  VLDQDQKEIIDTNGAGDAFVGGFLSQLVSDKPLTECIRAGHYAASIIIRRTGCTFPEKPD
  FH
• Function: This enzyme catalyzes the transfer of gamma-phosphate from Adenosine triphosphate (ATP) to adenosine (Ado) leading to formation of Adenosine monophosphate (AMP).
• KEGG Pathway:
  Metabolic pathways (hsa01100)
  Purine metabolism (hsa00230)
• Reactome Pathway: Purine salvage (R-HSA-74217)

Molecular Interaction Atlas (MIA) of This DME

1 Clinical Trial Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TRICIRIBINE	DM8IC5H	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[11]

Molecular Expression Atlas (MEA) of This DME

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	7.15E-13	3.51E-01	1.06E+00
Alopecia	ED70	Skin from scalp	2.10E-01	-7.44E-02	-3.80E-01
Alzheimer's disease	8A20	Entorhinal cortex	3.95E-03	-8.42E-02	-4.23E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	9.97E-01	-2.95E-01	-4.25E-01
Aortic stenosis	BB70	Calcified aortic valve	5.90E-01	8.99E-02	1.42E-01
Apnea	7A40	Hyperplastic tonsil	3.29E-01	-4.83E-01	-1.22E+00
Arthropathy	FA00-FA5Z	Peripheral blood	9.67E-01	-4.87E-02	-1.30E-01
Asthma	CA23	Nasal and bronchial airway	6.84E-08	5.61E-01	7.23E-01
Atopic dermatitis	EA80	Skin	5.26E-02	-2.37E-01	-1.01E+00
Autism	6A02	Whole blood	2.22E-01	-1.46E-02	-4.68E-02
Autoimmune uveitis	9A96	Peripheral monocyte	7.58E-04	-7.67E-01	-8.50E-01
Autosomal dominant monocytopenia	4B04	Whole blood	6.78E-04	-1.30E+00	-1.90E+00
Bacterial infection of gingival	1C1H	Gingival tissue	1.98E-13	-7.46E-01	-1.48E+00
Batten disease	5C56.1	Whole blood	4.17E-01	-6.22E-02	-3.15E-01
Behcet's disease	4A62	Peripheral blood	8.91E-01	-2.34E-01	-6.02E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	3.27E-01	-3.55E-02	-1.81E-01
Bladder cancer	2C94	Bladder tissue	3.09E-01	2.25E-02	6.16E-02
Breast cancer	2C60-2C6Z	Breast tissue	5.91E-01	-1.19E-02	-2.36E-02
Cardioembolic stroke	8B11.20	Whole blood	5.40E-04	-4.33E-01	-1.20E+00
Cervical cancer	2C77	Cervical tissue	8.35E-01	-9.87E-02	-1.69E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	8.34E-01	-1.55E-01	-2.18E-01
Chronic hepatitis C	1E51.1	Whole blood	2.80E-01	5.09E-02	2.91E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	4.88E-01	9.56E-02	2.94E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	6.64E-01	5.70E-03	2.46E-02
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	9.22E-02	2.55E-01	8.17E-01
Colon cancer	2B90	Colon tissue	1.70E-58	8.48E-01	1.99E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	3.19E-01	-4.66E-01	-7.50E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	1.13E-01	3.34E-01	5.84E-01
Endometriosis	GA10	Endometrium tissue	2.06E-02	-4.60E-01	-7.26E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	5.80E-01	-1.35E-02	-8.28E-02
Familial hypercholesterolemia	5C80.00	Whole blood	5.23E-02	3.48E-01	8.25E-01
Gastric cancer	2B72	Gastric tissue	4.22E-03	7.84E-01	5.46E+00
Glioblastopma	2A00.00	Nervous tissue	1.39E-61	4.62E-01	1.18E+00
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	3.20E-03	6.75E-01	6.46E+00
Glioma	2A00.0Y-2A00.0Z	White matter tissue	4.19E-01	-4.24E-02	-7.73E-02
Head and neck cancer	2D42	Head and neck tissue	2.77E-09	5.22E-01	6.43E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	7.98E-01	3.55E-02	1.10E-01
Huntington's disease	8A01.10	Whole blood	9.07E-01	9.84E-02	2.13E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	1.85E-01	-1.97E-01	-1.70E+00
Immunodeficiency	4A00-4A20	Peripheral blood	1.40E-03	4.05E-01	1.89E+00
Influenza	1E30	Whole blood	5.57E-01	-5.50E-01	-7.96E-01
Interstitial cystitis	GC00.3	Bladder tissue	3.80E-03	-7.43E-01	-3.33E+00
Intracranial aneurysm	8B01.0	Intracranial artery	1.18E-01	2.06E-01	5.29E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	8.70E-01	1.08E-02	3.29E-02
Ischemic stroke	8B11	Peripheral blood	5.42E-01	6.21E-02	1.53E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	1.86E-04	-1.02E-01	-3.05E-01
Lateral sclerosis	8B60.4	Skin	1.77E-01	3.73E-01	7.24E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	2.37E-01	-3.58E-01	-6.86E-01
Liver cancer	2C12.0	Liver tissue	4.25E-18	-1.17E+00	-2.08E+00
Liver failure	DB99.7-DB99.8	Liver tissue	8.73E-05	-1.93E+00	-6.54E+00
Lung cancer	2C25	Lung tissue	5.57E-04	1.21E-01	2.94E-01
Lupus erythematosus	4A40	Whole blood	1.50E-01	-5.36E-02	-1.03E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	7.26E-01	1.63E-02	8.94E-02
Major depressive disorder	6A70-6A7Z	Whole blood	1.40E-01	-1.20E-01	-3.43E-01
Melanoma	2C30	Skin	4.32E-03	-3.88E-01	-7.03E-01
Multiple myeloma	2A83.1	Peripheral blood	6.61E-01	-2.77E-01	-2.35E-01
Multiple myeloma	2A83.1	Bone marrow	6.36E-08	6.36E-01	5.11E+00
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	1.03E-01	-1.52E-01	-5.34E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	3.24E-01	-1.45E-01	-2.75E-01
Myelofibrosis	2A20.2	Whole blood	5.26E-01	-8.02E-02	-2.25E-01
Myocardial infarction	BA41-BA50	Peripheral blood	1.13E-01	-2.77E-01	-4.56E-01
Myopathy	8C70.6	Muscle tissue	7.66E-01	-2.73E-02	-1.78E-01
Neonatal sepsis	KA60	Whole blood	5.71E-09	-4.49E-01	-1.14E+00
Neuroectodermal tumour	2A00.11	Brain stem tissue	5.43E-09	8.24E-01	3.24E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	1.46E-02	3.71E-01	1.47E+00
Obesity related type 2 diabetes	5A11	Omental adipose tissue	7.68E-02	-2.33E-01	-7.27E-01
Olive pollen allergy	CA08.00	Peripheral blood	7.52E-01	-3.48E-02	-6.17E-02
Oral cancer	2B6E	Oral tissue	5.34E-03	3.25E-01	4.45E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	5.99E-01	3.98E-01	4.20E-01
Osteoporosis	FB83.1	Bone marrow	1.79E-02	-6.31E-01	-1.75E+00
Ovarian cancer	2C73	Ovarian tissue	1.22E-06	1.13E+00	3.75E+00
Pancreatic cancer	2C10	Pancreas	3.07E-04	9.82E-02	5.45E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	1.16E-01	-1.26E-01	-2.93E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	1.56E-02	-3.96E-01	-1.48E+00
Pituitary cancer	2D12	Pituitary tissue	1.03E-01	9.18E-02	4.07E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	2.96E-01	9.78E-02	4.63E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	9.39E-03	2.06E-01	1.05E+00
Polycythemia vera	2A20.4	Whole blood	1.76E-09	-4.89E-01	-1.44E+00
Pompe disease	5C51.3	Biceps muscle	8.83E-04	3.54E-01	2.26E+00
Preterm birth	KA21.4Z	Myometrium	3.20E-01	-2.48E-01	-6.52E-01
Prostate cancer	2C82	Prostate	1.88E-01	9.15E-02	1.42E-01
Psoriasis	EA90	Skin	1.93E-05	2.28E-01	5.65E-01
Rectal cancer	2B92	Rectal colon tissue	4.26E-06	6.97E-01	3.76E+00
Renal cancer	2C90-2C91	Kidney	8.22E-01	-1.62E-01	-4.71E-01
Retinoblastoma	2D02.2	Uvea	2.14E-02	3.42E-01	1.53E+00
Rheumatoid arthritis	FA20	Synovial tissue	4.52E-03	8.65E-01	1.38E+00
Rhinovirus infection	CA42.1	Nasal epithelium tissue	8.38E-01	-1.47E-02	-8.64E-02
Schizophrenia	6A20	Prefrontal cortex	4.49E-01	-7.38E-03	-1.61E-02
Schizophrenia	6A20	Superior temporal cortex	6.73E-01	-2.71E-02	-1.74E-01
Scleroderma	4A42.Z	Whole blood	2.88E-04	-2.89E-01	-1.75E+00
Seizure	8A60-8A6Z	Whole blood	2.43E-01	3.12E-01	5.75E-01
Sensitive skin	EK0Z	Skin	4.85E-01	9.94E-02	4.66E-01
Sepsis with septic shock	1G41	Whole blood	8.87E-65	-7.56E-01	-2.31E+00
Shwachman-Diamond syndrome	3A70.0	Bone marrow	3.82E-01	-1.43E-01	-5.27E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	1.36E-02	-5.09E-01	-9.37E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	1.53E-01	-1.77E-01	-2.50E+00
Sjogren's syndrome	4A43.2	Salivary gland tissue	9.52E-01	8.71E-03	1.72E-01
Skin cancer	2C30-2C3Z	Skin	1.52E-43	-8.65E-01	-1.94E+00
Thrombocythemia	3B63	Whole blood	1.17E-01	-2.18E-01	-6.32E-01
Thrombocytopenia	3B64	Whole blood	2.98E-01	-5.40E-01	-8.08E-01
Thyroid cancer	2D10	Thyroid	4.70E-39	8.90E-01	2.16E+00
Tibial muscular dystrophy	8C75	Muscle tissue	5.81E-02	1.69E-01	7.31E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	4.55E-02	-2.77E-01	-1.73E+00
Type 2 diabetes	5A11	Liver tissue	9.12E-05	5.50E-01	5.02E+00
Ureter cancer	2C92	Urothelium	3.28E-01	-4.60E-02	-2.18E-01
Uterine cancer	2C78	Endometrium tissue	2.00E-05	5.11E-01	5.69E-01
Vitiligo	ED63.0	Skin	3.42E-01	-6.75E-02	-5.26E-01

The Drug Therapeutic Target (DTT) Role of This DME

• DME DTT Name: Adenosine kinase (ADK) DTT Info
• DME DTT Type: Clinical trial

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GP-3269	DM035LO	Convulsion	8A68.Z	Phase 1	[1]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-134974	DMRWDX5	Epilepsy	8A60-8A68	Terminated	[2]
ABT-702	DMYJMV9	Pain	MG30-MG3Z	Terminated	[3]
GP-683	DMPODL9	Pain	MG30-MG3Z	Terminated	[4]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
5'-iodotubercidin	DML5ZEJ	Discovery agent	N.A.	Investigative	[5]
5-iodo,5'-deoxytubercidin	DMVT2LW	Discovery agent	N.A.	Investigative	[6]
6-Benzylthioinosine	DMNXGZP	Discovery agent	N.A.	Investigative	[7]
GP515	DMRUIX3	Discovery agent	N.A.	Investigative	[8]
Iodotubercidin	DMQMH6S	Discovery agent	N.A.	Investigative	[9]
MB-03966	DM9KLQC	Epileptic seizures	8A61-8A6Z	Investigative	[10]

References

• [1] Adenosine kinase inhibitors. 6. Synthesis, water solubility, and antinociceptive activity of 5-phenyl-7-(5-deoxy-beta-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidines substituted at C4 with glycinamides andrelated compounds. J Med Chem. 2005 Dec 1;48(24):7808-20.
• [2] Effects of A-134974, a novel adenosine kinase inhibitor, on carrageenan-induced inflammatory hyperalgesia and locomotor activity in rats: evaluation of the sites of action. J Pharmacol Exp Ther. 2001Feb;296(2):501-9.
• [3] ABT-702, an adenosine kinase inhibitor, attenuates inflammation in diabetic retinopathy. Life Sci. 2013 Jul 30;93(2-3):78-88.
• [4] The effect of GP683, an adenosine kinase inhibitor, on the desflurane anesthetic requirement in dogs. Anesth Analg. 1997 Sep;85(3):675-80.
• [5] Inhibition of adenosine kinase attenuates interleukin-1- and lipopolysaccharide-induced alterations in articular cartilage metabolism. Osteoarthritis Cartilage. 2005 Mar;13(3):250-7.
• [6] Crystal structures of human adenosine kinase inhibitor complexes reveal two distinct binding modes. J Med Chem. 2006 Nov 16;49(23):6726-31.
• [7] Structure-activity relationships of carbocyclic 6-benzylthioinosine analogues as subversive substrates of Toxoplasma gondii adenosine kinase. Bioorg Med Chem. 2010 May 15;18(10):3403-12.
• [8] Adenosine kinase inhibitor GP515 improves experimental colitis in mice. J Pharmacol Exp Ther. 2001 Jan;296(1):99-105.
• [9] Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
• [10] Engineered Adenosine-Releasing Cells for Epilepsy Therapy: Human Mesenchymal Stem Cells and Human Embryonic Stem Cells. Neurotherapeutics. 2009 April; 6(2): 278-283.
• [11] Phosphorylation of triciribine is necessary for activity against HIV type 1. AIDS Res Hum Retroviruses. 1998 Oct 10;14(15):1315-22.