Details of the Drug

General Information of Drug (ID: DMV2OJX)

• Drug Name: Guanosine-5'-Triphosphate

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 4:
  Molecular Weight (mw); 523.179
  Logarithm of the Partition Coefficient (xlogp); -5.7
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 8
  Hydrogen Bond Acceptor Count (hbondacc); 16
• Chemical Identifiers:
  Formula: C10H16N5O14P3
  IUPAC Name: [[(2R,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate
  Canonical SMILES: C1=NC2=C(N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O)O)N=C(NC2=O)N
  InChI: InChI=1S/C10H16N5O14P3/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(27-9)1-26-31(22,23)29-32(24,25)28-30(19,20)21/h2-3,5-6,9,16-17H,1H2,(H,22,23)(H,24,25)(H2,19,20,21)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1
  InChIKey: XKMLYUALXHKNFT-UUOKFMHZSA-N
• Cross-matching ID:
  PubChem CID: 135398633
  ChEBI ID: CHEBI:15996
  CAS Number: 86-01-1
  DrugBank ID: DB04137
  TTD ID: D0EQ4T

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial GTP-binding protein YihA (Bact engB)	TTO3MV6	ENGB_ECOLI	Inhibitor	[2]
GTP cyclohydrolase-I (GCH1)	TTLSWP6	GCH1_HUMAN	Inhibitor	[2]
Virus RNA-dependent RNA polymerase (Viru RdRP)	TTSUKYD	POLG_HCVJA	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Alpha-(1,6)-fucosyltransferase (FUT8)	OTJJCVG1	FUT8_HUMAN	Gene/Protein Processing	[3]
Amyloid-beta precursor protein (APP)	OTKFD7R4	A4_HUMAN	Protein Interaction/Cellular Processes	[4]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Biotransformations	[5]
Glycophorin-A (GYPA)	OTABU4YV	GLPA_HUMAN	Gene/Protein Processing	[6]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Biotransformations	[7]
Histamine H3 receptor (HRH3)	OT7GF3AI	HRH3_HUMAN	Protein Interaction/Cellular Processes	[8]
Leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2)	OTLS7C99	LRRK2_HUMAN	Drug Response	[9]
Protein-glutamine gamma-glutamyltransferase 2 (TGM2)	OT6MFOWF	TGM2_HUMAN	Protein Interaction/Cellular Processes	[10]
Transforming protein RhoA (RHOA)	OT6YOJ9N	RHOA_HUMAN	Drug Response	[11]

Molecular Expression Atlas of This Drug

• The Studied Disease: Discovery agent
• ICD Disease Classification: N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
GTP cyclohydrolase-I (GCH1)	DTT	GCH1	3.38E-02	-1.59	-1.53

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: 1742).
• [2] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [3] Chemical modifications of alpha1,6-fucosyltransferase define amino acid residues of catalytic importance. Biochimie. 2003 Mar-Apr;85(3-4):303-10. doi: 10.1016/s0300-9084(03)00074-9.
• [4] High-energy compounds promote physiological processing of Alzheimer's amyloid- precursor protein and boost cell survival in culture. J Neurochem. 2012 Nov;123(4):525-31. doi: 10.1111/j.1471-4159.2012.07923.x. Epub 2012 Sep 21.
• [5] Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells. Cancer Res. 1988 Sep 1;48(17):4926-32.
• [6] GTP induces S-phase cell-cycle arrest and inhibits DNA synthesis in K562 cells but not in normal human peripheral lymphocytes. J Biochem Mol Biol. 2006 Sep 30;39(5):492-501. doi: 10.5483/bmbrep.2006.39.5.492.
• [7] A KRAS GTPase K104Q Mutant Retains Downstream Signaling by Offsetting Defects in Regulation. J Biol Chem. 2017 Mar 17;292(11):4446-4456. doi: 10.1074/jbc.M116.762435. Epub 2017 Jan 30.
• [8] Discovery and characterization of 6-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2H-pyridazin-3-one (CEP-26401, irdabisant): a potent, selective histamine H3 receptor inverse agonist. J Med Chem. 2011 Jul 14;54(13):4781-92. doi: 10.1021/jm200401v. Epub 2011 Jun 2.
• [9] Arsenite stress down-regulates phosphorylation and 14-3-3 binding of leucine-rich repeat kinase 2 (LRRK2), promoting self-association and cellular redistribution. J Biol Chem. 2014 Aug 1;289(31):21386-400. doi: 10.1074/jbc.M113.528463. Epub 2014 Jun 18.
• [10] Overexpression of transglutaminase 2 accelerates the erythroid differentiation of human chronic myelogenous leukemia K562 cell line through PI3K/Akt signaling pathway. FEBS Lett. 2004 Nov 19;577(3):361-6. doi: 10.1016/j.febslet.2004.10.031.
• [11] Antioxidants prevent the RhoA inhibition evoked by crocidolite asbestos in human mesothelial and mesothelioma cells. Am J Respir Cell Mol Biol. 2011 Sep;45(3):625-31.