Details of the Drug

General Information of Drug (ID: DM1RBYG)

• Drug Name: Nitric Oxide
• 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
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 30.006
  Topological Polar Surface Area (xlogp); 0.2
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 1
• ADMET Property:
  Half-life: The concentration or amount of drug in body reduced by one-half in 2 - 6 seconds [5]
  Metabolism: The drug is metabolized via pulmonary capillary bed [6]
• Chemical Identifiers:
  Formula: NO
  IUPAC Name: nitric oxide
  Canonical SMILES: [N]=O
  InChI: InChI=1S/NO/c1-2
  InChIKey: MWUXSHHQAYIFBG-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 145068
  ChEBI ID: CHEBI:16480
  CAS Number: 10102-43-9
  DrugBank ID: DB00435
  TTD ID: D0A5FM
  VARIDT ID: DR01184

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Guanylate cyclase (GC)	TT6HPVC	NOUNIPROTAC	Stimulator	[7]
Soluble guanylate cyclase (GCS)	TT23PYC	GCYA1_HUMAN; GCYB1_HUMAN	Stimulator	[8]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Alanine/serine/cysteine/threonine transporter 2 (SLC1A5)	DTW7AE3	AAAT_HUMAN	Substrate	[9]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Nitric Oxide (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Prilocaine	DMI7DZ2	Major	Increased risk of methemoglobinemia by the combination of Nitric Oxide and Prilocaine.	Pain [MG30-MG3Z]	[23]

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] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [6] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [7] Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart. Mol Cell Biochem. 2010 Jan;333(1-2):191-201.
• [8] Nitric oxide and nitrovasodilators: similarities, differences, and interactions. Am J Cardiol. 1996 May 30;77(13):2C-7C.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Activators of soluble guanylate cyclase for the treatment of male erectile dysfunction. Int J Impot Res. 2002 Feb;14(1):8-14.
• [18] Stimulators and activators of soluble guanylate cyclase: review and potential therapeutic indications.Crit Care Res Pract.2012;2012:290805.
• [19] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [20] Curcumin ameliorates high glucose-induced acute vascular endothelial dysfunction in rat thoracic aorta. Clin Exp Pharmacol Physiol. 2009 Dec;36(12):1177-82.
• [21] Activation of soluble guanylyl cyclase by the nitrovasodilator 3-morpholinosydnonimine involves formation of S-nitrosoglutathione. Mol Pharmacol. 1998 Jul;54(1):207-12.
• [22] Clinical pipeline report, company report or official report of Cyclerion Therapeutics.
• [23] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".