Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTL732K)

• DTT Name: Adenosine kinase (ADK)
• Synonyms: Adenosine 5'-phosphotransferase; AK
• Gene Name: ADK
• DTT Type: Clinical trial target; [1]
• Related Disease: Epilepsy/seizure [ICD-11: 8A61-8A6Z]
• BioChemical Class: Kinase
• UniProt ID: ADK_HUMAN
• TTD ID: T91661
• EC Number: EC 2.7.1.20
• Sequence:
  MAAAEEEPKPKKLKVEAPQALRENILFGMGNPLLDISAVVDKDFLDKYSLKPNDQILAED
  KHKELFDELVKKFKVEYHAGGSTQNSIKVAQWMIQQPHKAATFFGCIGIDKFGEILKRKA
  AEAHVDAHYYEQNEQPTGTCAACITGDNRSLIANLAAANCYKKEKHLDLEKNWMLVEKAR
  VCYIAGFFLTVSPESVLKVAHHASENNRIFTLNLSAPFISQFYKESLMKVMPYVDILFGN
  ETEAATFAREQGFETKDIKEIAKKTQALPKMNSKRQRIVIFTQGRDDTIMATESEVTAFA
  VLDQDQKEIIDTNGAGDAFVGGFLSQLVSDKPLTECIRAGHYAASIIIRRTGCTFPEKPD
  FH
• Function: Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides. ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives.
• Reactome Pathway: Purine salvage (R-HSA-74217)
• BioCyc Pathway: MetaCyc:HS08097-MON

Molecular Interaction Atlas (MIA) of This DTT

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]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Adenosine kinase (ADK) DME Info
• Gene Name: ADK

1 Clinical Trial Drug(s) Metabolized by This DTT

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

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.