Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM1RBYG)

• Drug Name: Nitric Oxide Drug Info
• Synonyms: Nitric oxide; nitric oxide; nitrogen monoxide; Mononitrogen monoxide; 10102-43-9; nitrogen monooxide; nitrogen protoxide; nitrosyl; Nitrosyl radical; EDRF; CHEBI:16480; endothelium-derived relaxing factor; monoxyde d'azote; oxoazanyl; oxyde azotique; oxido nitrico; Stickstoffmonoxid; Nitric oxide trimer; monoxido de nitrogeno; Stickstoff(II)-oxid; Nitric oxide (JAN); INOmax (TN); oxido de nitrogeno(II); Nitrosoradical; [NO]; oxidonitrogen(); Nitrogen(II) oxide; OHM 11771; AC1L3QHF; Nitric oxide, 985%; DTXSID1020938; CHEMBL1200689; CTK0H7679; ()NO; HNO; INOmax; Nitrosyl; Nitroxyl; Oxoazanyl; Stickmonoxyd; Endogenous Nitrate Vasodilator; Monoxido de nitrogeno; Nitrogen monooxide; Nitrogen monoxide; Nitrosyl hydride; Nitroxide radical; Oxido nitrico; Oxyde azotique; Oxyde nitrique [French]; Stickmonoxyd [German]; Bioxyde d'azote; Bioxyde d'azote [French]; Endothelium-Derived Nitric Oxide; Monoxide, Mononitrogen; Monoxide, Nitrogen; Monoxyde d'azote; NITRIC-OXIDE; NO(); Nitrate Vasodilator, Endogenous; Nitric Oxide, Endothelium Derived; Nitric oxide 10% by volume or more; Nitric oxide, compressed [UN1660] [Poison gas]; Nitrogen oxide (NO); Oxide, Nitric; Oxido de nitrogeno(II); Oxidonitrogen(); Vasodilator, Endogenous Nitrate; Nitric Oxide, Endothelium-Derived; Nitrosyl hydride ((NO)H); Endothelium-derived relaxing factor (EDRF)

Indication

Disease Entry	ICD 11	Status	REF
Respiratory failure	CB41	Approved	[1] , [2]
Solid tumour/cancer	2A00-2F9Z	Phase 3	[1] , [3]
Tinea pedis	1F28.2	Discontinued in Phase 2	[4]

• Therapeutic Class: Bronchodilator Agents
• Cross-matching ID:
  PubChem CID: 145068
  ChEBI ID: CHEBI:16480
  CAS Number: CAS 10102-43-9
  TTD Drug ID: DM1RBYG
  VARIDT Drug ID: DR01184

Molecule-Related Drug Atlas

Drug(s) Transported By Alanine/serine/cysteine/threonine transporter 2 (SLC1A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aciclovir	DMYLOVR	Virus infection	1A24-1D9Z	Approved	[8]
Ganciclovir	DM1MBYQ	Virus infection	1A24-1D9Z	Approved	[8]
Levacecarnine HCL	DMJBOCR	Cognitive impairment	6D71	Approved	[9]
Glycine	DMIOZ29	Malnutrition	5B50-5B71	Approved	[10]
L-glutamine	DM69G8X	Short bowel syndrome	KB89.1	Approved	[11]
Valaciclovir	DMHKS94	Virus infection	1A24-1D9Z	Approved	[12]
Valganciclovir	DMS2IUH	Virus infection	1A24-1D9Z	Approved	[13]
D-Serine	DM3YH4I	N. A.	N. A.	Phase 4	[14]
L-threonine	DMFHTBX	Discovery agent	N.A.	Investigative	[14]

Drug(s) Targeting Soluble guanylate cyclase (GCS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nitroglycerin	DMQ2491	Angina pectoris	BA40	Approved	[15]
Sodium nitroprusside	DMGA9X0	Hypertension	BA00-BA04	Approved	[16]
IW-1973	DMK2T7J	Heart failure	BD10-BD13	Phase 2	[17]
(5-(1-benzyl-1H-indazol-3-yl)furan-2-yl)methanol	DM15P2G	Discovery agent	N.A.	Investigative	[15]

Drug(s) Targeting Guanylate cyclase (GC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Isosorbide dinitrate	DMBI4JG	Anal fissure	DB50.0	Approved	[5]
Methylene blue	DMJAPE7	Acquired methemoglobinemia	3A93	Approved	[18]
Isosorbide mononitrate	DMYLMU0	Hydrocephalus	8D64	Approved	[5]
Erythrityl Tetranitrate	DMFGQ2S	Angina pectoris	BA40	Approved	[5]
Pirsidomine	DMHI6GE	Angina pectoris	BA40	Phase 2	[19]
IW-1701	DM457XO	Sickle-cell disorder	3A51	Phase 2	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Guanylate cyclase (GC)	TT6HPVC	NOUNIPROTAC	Stimulator	[5]
Soluble guanylate cyclase (GCS)	TT23PYC	GCYA1_HUMAN; GCYB1_HUMAN	Stimulator	[6]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Alanine/serine/cysteine/threonine transporter 2 (SLC1A5)	DTW7AE3	AAAT_HUMAN	Substrate	[7]

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: 2509).
• [2] Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome. Expert Opin Emerg Drugs. 2007 Sep;12(3):461-77.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024215)
• [5] Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart. Mol Cell Biochem. 2010 Jan;333(1-2):191-201.
• [6] Nitric oxide and nitrovasodilators: similarities, differences, and interactions. Am J Cardiol. 1996 May 30;77(13):2C-7C.
• [7] Functional regulation of Na+-dependent neutral amino acid transporter ASCT2 by S-nitrosothiols and nitric oxide in Caco-2 cells. FEBS Lett. 2005 Apr 25;579(11):2499-506.
• [8] Amino Acid Transporter ATB0,+ as a delivery system for drugs and prodrugs. Curr Drug Targets Immune Endocr Metabol Disord. 2005 Dec;5(4):357-64.
• [9] A polarized localization of amino acid/carnitine transporter B(0,+) (ATB(0,+)) in the blood-brain barrier. Biochem Biophys Res Commun. 2008 Nov 14;376(2):267-70.
• [10] Transport of butyryl-L-carnitine, a potential prodrug, via the carnitine transporter OCTN2 and the amino acid transporter ATB(0,+). Am J Physiol Gastrointest Liver Physiol. 2007 Nov;293(5):G1046-53.
• [11] High-affinity glutamate transporter GLAST/EAAT1 regulates cell surface expression of glutamine/neutral amino acid transporter ASCT2 in human fetal astrocytes. Neurochem Int. 2006 May-Jun;48(6-7):611-5.
• [12] Transport of amino acid-based prodrugs by the Na+- and Cl(-) -coupled amino acid transporter ATB0,+ and expression of the transporter in tissues amenable for drug delivery. J Pharmacol Exp Ther. 2004 Mar;308(3):1138-47.
• [13] Transport of amino acid esters and the amino-acid-based prodrug valganciclovir by the amino acid transporter ATB(0,+). Pharm Res. 2004 Jul;21(7):1303-10.
• [14] D-Serine Is a Substrate for Neutral Amino Acid Transporters ASCT1/SLC1A4 and ASCT2/SLC1A5, and Is Transported by Both Subtypes in Rat Hippocampal Astrocyte Cultures. PLoS One. 2016 Jun 7;11(6):e0156551.
• [15] Activators of soluble guanylate cyclase for the treatment of male erectile dysfunction. Int J Impot Res. 2002 Feb;14(1):8-14.
• [16] Stimulators and activators of soluble guanylate cyclase: review and potential therapeutic indications.Crit Care Res Pract.2012;2012:290805.
• [17] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [18] Curcumin ameliorates high glucose-induced acute vascular endothelial dysfunction in rat thoracic aorta. Clin Exp Pharmacol Physiol. 2009 Dec;36(12):1177-82.
• [19] Activation of soluble guanylyl cyclase by the nitrovasodilator 3-morpholinosydnonimine involves formation of S-nitrosoglutathione. Mol Pharmacol. 1998 Jul;54(1):207-12.
• [20] Clinical pipeline report, company report or official report of Cyclerion Therapeutics.