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

General Information of Drug (ID: DM01SR6)

• Drug Name: L-NAME Drug Info
• Synonyms: N-Nitroarginine methyl ester; NG-NITROARGININE METHYL ESTER; N(G)-Nitroarginine methyl ester; N-Nitro-L-arginine methylester; Ngamma-Nitro-L-arginine methyl ester; N(G)-Nitro-L-arginine methyl ester; N(sup G)-Nitro-L-arginine methyl ester; N-omega-Nitro-O-arginine methyl ester; Methyl (2S)-2-amino-5-[[amino(nitramido)methylidene]amino]pentanoate; Methyl N5-(N'-nitrocarbamimidoyl)-L-ornithinate; N(5)-(Imino(nitroamino)methyl)-L-ornithine methyl ester; N-.omega.-Nitro-O-arginine methyl ester; L-Ornithine, N(5)-(imino(nitroamino)methyl)-, methyl ester; Methyl (2S)-2-amino-5-[(amino-nitramido-methylidene)amino]pentanoate

Indication

Disease Entry	ICD 11	Status	REF
Hypertension	BA00-BA04	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 39836
  ChEBI ID: CHEBI:7549
  CAS Number: CAS 50903-99-6
  TTD Drug ID: DM01SR6

Molecule-Related Drug Atlas

Drug(s) Targeting Nitric-oxide synthase endothelial (NOS3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tilarginine acetate	DMZBGI8	Myocardial infarction	BA41-BA43	Phase 3	[4]
ACCLAIM	DM0FGDO	Angina pectoris	BA40	Phase 2	[5]
VAS-203	DMKU93J	Brain injury	NA07.Z	Phase 2	[6]
MTR105	DMT0K4F	Hypotension	BA20-BA21	Phase 2	[7]
Autologous cell based gene therapy	DMQA1VT	Pulmonary hypertension	BB01	Phase 1	[8]
L-NIL	DM6Y49D	N. A.	N. A.	Terminated	[9]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[10]
2-Methyl-2,4-Pentanediol	DMD45CU	Discovery agent	N.A.	Investigative	[10]
Heme	DMGC287	Discovery agent	N.A.	Investigative	[11]
2-Propanol, Isopropanol	DML5O0H	Discovery agent	N.A.	Investigative	[10]

Drug(s) Affected By Nitric oxide synthase 3 (NOS3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[12]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[13]
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[14]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[15]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[16]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[17]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[19]
Fructose	DM43AN2	Vomiting	MD90	Approved	[20]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Nitric-oxide synthase endothelial (NOS3)	TTCM4B3	NOS3_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Nitric oxide synthase 3 (NOS3)	OTLDT7NR	NOS3_HUMAN	Gene/Protein Processing	[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: 5213).
• [2] Counter-regulation by atorvastatin of gene modulations induced by L-NAME hypertension is associated with vascular protection. Vascul Pharmacol. 2009 Oct;51(4):253-61.
• [3] Folic acid attenuates cobalt chloride-induced PGE(2) production in HUVECs via the NO/HIF-1alpha/COX-2 pathway. Biochem Biophys Res Commun. 2017 Aug 19;490(2):567-573. doi: 10.1016/j.bbrc.2017.06.079. Epub 2017 Jun 15.
• [4] Effect of tilarginine acetate in patients with acute myocardial infarction and cardiogenic shock: the TRIUMPH randomized controlled trial. JAMA. 2007 Apr 18;297(15):1657-66.
• [5] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [6] Nitric oxide synthase inhibition with the antipterin VAS203 improves outcome in moderate and severe traumatic brain injury: a placebo-controlled randomized Phase IIa trial (NOSTRA). J Neurotrauma. 2014 Oct 1;31(19):1599-606.
• [7] Nitric oxide synthase inhibitor (MTR-105) during open-heart surgery. A pilot double-blind placebo-controlled study of hemodynamic effects and safety. Cardiology. 2008;111(3):181-7.
• [8] Feasibility of using autologous transplantation to evaluate hematopoietic stem cell-based gene therapy strategies in transgenic mouse models of human disease. Mol Ther. 2002 Sep;6(3):422-8.
• [9] Discovery of a series of aminopiperidines as novel iNOS inhibitors. Bioorg Med Chem Lett. 2008 Jan 1;18(1):336-43.
• [10] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [11] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [12] Protective effects of S-carvedilol on doxorubicin-induced damages to human umbilical vein endothelial cells and rats. J Appl Toxicol. 2019 Aug;39(8):1233-1244. doi: 10.1002/jat.3809. Epub 2019 May 7.
• [13] Oxidative stress in kidney transplant patients with calcineurin inhibitor-induced hypertension: effect of ramipril. J Cardiovasc Pharmacol. 2002 Oct;40(4):625-31.
• [14] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [15] Hydrogen peroxide decreases endothelial nitric oxide synthase promoter activity through the inhibition of Sp1 activity. DNA Cell Biol. 2009 Mar;28(3):119-29.
• [16] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [17] Simvastatin inhibits cigarette smoking-induced emphysema and pulmonary hypertension in rat lungs. Am J Respir Crit Care Med. 2005 Oct 15;172(8):987-93. doi: 10.1164/rccm.200501-041OC. Epub 2005 Jul 7.
• [18] A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase. Nitric Oxide. 2005 Mar;12(2):97-104.
• [19] The thiazolidinedione drug troglitazone up-regulates nitric oxide synthase expression in vascular endothelial cells. J Diabetes Complications. 2006 Sep-Oct;20(5):336-42.
• [20] Fructose induces the inflammatory molecule ICAM-1 in endothelial cells. J Am Soc Nephrol. 2008 Sep;19(9):1712-20.
• [21] Upregulation of nitric oxide production in vascular endothelial cells by all-trans retinoic acid through the phosphoinositide 3-kinase/Akt pathway. Circulation. 2005 Aug 2;112(5):727-36. doi: 10.1161/CIRCULATIONAHA.104.500959. Epub 2005 Jul 25.