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

General Information of Drug (ID: DMLZT64)

• Drug Name: 1400W Drug Info
• Synonyms: N-(3-(Aminomethyl)benzyl)acetamidine; N-(3-(AMINOMETHYL)BENZYL)ACETAMIDINE; 180001-34-7; N-(3-(aminomethyl)benzyl)-acetamidine; n-[3-(aminomethyl)benzyl]ethanimidamide; CHEMBL107251; CHEBI:90721; N-{[3-(aminomethyl)phenyl]methyl}ethanimidamide; RODUKNYOEVZQPR-UHFFFAOYSA-N; n-[3-(aminomethyl)benzyl]acetamidine; N-(3-(aminomethyl)benzyl)acetimidamide; N-(3-Aminomethyl-benzyl)-acetamidine; CHEMBL544788; 14W; N-[[3-(Aminomethyl)phenyl]methyl]ethanimidamide; Bio1_001405; Tocris-1415; AC1Q4SXP; AC1L1BGT; Lopac-W-4262; W 1400; SCHEMBL4467; Lopac0_001258; W 1400; N-(3-(Aminomethyl)Benzyl)Acetamidine; N-(3-(aminomethyl)-benzyl)acetamidine

Indication

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

• Cross-matching ID:
  PubChem CID: 1433
  ChEBI ID: CHEBI:90721
  CAS Number: CAS 180001-34-7
  TTD Drug ID: DMLZT64

Molecule-Related Drug Atlas

Drug(s) Targeting Nitric-oxide synthase inducible (NOS2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[4]
SD-6010	DM9DEYL	Osteoarthritis	FA00-FA05	Phase 3	[5]
MPL-S	DMNDCFY	Endotoxic shock	1G41	Phase 3	[6]
Pimagedine HCl	DMPWH30	Diabetic kidney disease	GB61.Z	Phase 2/3	[7]
GW274150	DMZMCB1	Asthma	CA23	Phase 2	[8]
BXT-51072	DMD8GNB	Cardiovascular disease	BA00-BE2Z	Phase 2	[9]
HP-228	DMNZ35F	Postoperative pain	MG30-MG3Z	Phase 2	[10]
CR-3294	DMHJEZS	Diarrhea	ME05.1	Phase 2	[11]
KD-7040	DME1WV2	Pain	MG30-MG3Z	Phase 2	[12]
LT-1951	DM5N04G	Coronary artery disease	BA80	Phase 1/2	[13]

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	[14]
L-NAME	DM01SR6	Hypertension	BA00-BA04	Phase 2	[15]
ACCLAIM	DM0FGDO	Angina pectoris	BA40	Phase 2	[16]
VAS-203	DMKU93J	Brain injury	NA07.Z	Phase 2	[17]
MTR105	DMT0K4F	Hypotension	BA20-BA21	Phase 2	[18]
Autologous cell based gene therapy	DMQA1VT	Pulmonary hypertension	BB01	Phase 1	[19]
L-NIL	DM6Y49D	N. A.	N. A.	Terminated	[20]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[21]
2-Methyl-2,4-Pentanediol	DMD45CU	Discovery agent	N.A.	Investigative	[21]
Heme	DMGC287	Discovery agent	N.A.	Investigative	[2]

Drug(s) Targeting Nitric-oxide synthase brain (NOS1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NXN-188	DMMBAIH	Migraine	8A80	Phase 2	[22]
NXN-462	DMWVBS2	Headache	8A80-8A84	Phase 2	[23]
L-NIL	DM6Y49D	N. A.	N. A.	Terminated	[20]
Alpha-D-Mannose	DMF5DLW	Discovery agent	N.A.	Investigative	[21]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[21]
Flavin-Adenine Dinucleotide	DM5S4GK	Discovery agent	N.A.	Investigative	[21]
Heme	DMGC287	Discovery agent	N.A.	Investigative	[2]
Formic Acid	DMNFZC6	Discovery agent	N.A.	Investigative	[21]
2'-Monophosphoadenosine 5'-Diphosphoribose	DME9S8M	Discovery agent	N.A.	Investigative	[21]
6-isobutyl-4-methylpyridin-2-amine	DM2XB68	Discovery agent	N.A.	Investigative	[24]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Nitric-oxide synthase brain (NOS1)	TTZUFI5	NOS1_HUMAN	Inhibitor	[2]
Nitric-oxide synthase endothelial (NOS3)	TTCM4B3	NOS3_HUMAN	Inhibitor	[2]
Nitric-oxide synthase inducible (NOS2)	TTF10I9	NOS2_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: 5102).
• [2] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [3] 1400W is a slow, tight binding, and highly selective inhibitor of inducible nitric-oxide synthase in vitro and in vivo. J Biol Chem. 1997 Feb 21;272(8):4959-63.
• [4] A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8.
• [5] A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee. Ann Rheum Dis. 2013 Feb;72(2):187-95.
• [6] Lipopolysaccharide and monophosphoryl lipid A differentially regulate interleukin-12, gamma interferon, and interleukin-10 mRNA production in murine macrophages. Infect Immun. 1997 Aug;65(8):3239-47.
• [7] Nitric oxide associated with iNOS expression inhibits acetylcholinesterase activity and induces memory impairment during acute hypobaric hypoxia. Brain Res. 2008 Sep 16;1230:138-49.
• [8] GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury. Kidney Int. 2003 Mar;63(3):853-65.
• [9] Shear stress induces iNOS expression in cultured smooth muscle cells: role of oxidative stress. Am J Physiol Cell Physiol. 2000 Dec;279(6):C1880-8.
• [10] HP-228, a novel synthetic peptide, inhibits the induction of nitric oxide synthase in vivo but not in vitro. J Pharmacol Exp Ther. 1995 Nov;275(2):584-91.
• [11] Efficacy of CR3294, a new benzamidine derivative, in the prevention of 5-fluorouracil-induced gastrointestinal mucositis and diarrhea in mice. Cancer Chemother Pharmacol. 2010 October; 66(5): 819-827.
• [12] WO patent application no. 2014,0214,08, Method for treating cancer by anticancer agent co-administration.
• [13] Critical role of L-arginine in endothelial cell survival during oxidative stress. Circulation. 2003 May 27;107(20):2607-14.
• [14] 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.
• [15] 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.
• [16] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] Discovery of a series of aminopiperidines as novel iNOS inhibitors. Bioorg Med Chem Lett. 2008 Jan 1;18(1):336-43.
• [21] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [22] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [23] ClinicalTrials.gov (NCT01748877) Efficacy, Tolerability, and Safety of NXN-462 in Patients With Post-Herpetic Neuralgia. U.S. National Institutes of Health.
• [24] Design and synthesis of 2-amino-4-methylpyridine analogues as inhibitors for inducible nitric oxide synthase and in vivo evaluation of [18F]6-(2-fl... J Med Chem. 2009 Apr 23;52(8):2443-53.