Details of the Drug

General Information of Drug (ID: DMRWDX5)

• Drug Name: A-134974
• Synonyms: a-134974; GTPL5130; CHEMBL1591918; ZINC3827162; SMP2_000021; NCGC00186045-01; A134974; A 134974

Indication

Disease Entry	ICD 11	Status	REF
Epilepsy	8A60-8A68	Terminated	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 375.17
  Topological Polar Surface Area (xlogp); -1.1
  Rotatable Bond Count (rotbonds); 1
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 6
• Chemical Identifiers:
  Formula: C11H14IN5O2
  IUPAC Name: (1S,2R,3S,5R)-3-amino-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol
  Canonical SMILES: C1[C@@H]([C@H]([C@H]([C@@H]1N2C=C(C3=C(N=CN=C32)N)I)O)O)N
  InChI: InChI=1S/C11H14IN5O2/c12-4-2-17(6-1-5(13)8(18)9(6)19)11-7(4)10(14)15-3-16-11/h2-3,5-6,8-9,18-19H,1,13H2,(H2,14,15,16)/t5-,6+,8+,9-/m0/s1
  InChIKey: NSXJHIFQIZKLGF-LWIVVEGESA-N
• Cross-matching ID:
  PubChem CID: 9885936
  TTD ID: D0S9XV

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adenosine kinase (ADK)	TTL732K	ADK_HUMAN	Inhibitor	[3]

References

• [1] 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: 5130).
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009094)
• [3] 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.
• [4] 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.
• [5] ABT-702, an adenosine kinase inhibitor, attenuates inflammation in diabetic retinopathy. Life Sci. 2013 Jul 30;93(2-3):78-88.
• [6] The effect of GP683, an adenosine kinase inhibitor, on the desflurane anesthetic requirement in dogs. Anesth Analg. 1997 Sep;85(3):675-80.
• [7] Adenosine kinase inhibitor GP515 improves experimental colitis in mice. J Pharmacol Exp Ther. 2001 Jan;296(1):99-105.
• [8] Inhibition of adenosine kinase attenuates interleukin-1- and lipopolysaccharide-induced alterations in articular cartilage metabolism. Osteoarthritis Cartilage. 2005 Mar;13(3):250-7.
• [9] Engineered Adenosine-Releasing Cells for Epilepsy Therapy: Human Mesenchymal Stem Cells and Human Embryonic Stem Cells. Neurotherapeutics. 2009 April; 6(2): 278-283.
• [10] Crystal structures of human adenosine kinase inhibitor complexes reveal two distinct binding modes. J Med Chem. 2006 Nov 16;49(23):6726-31.
• [11] 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.
• [12] Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.