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

General Information of Drug (ID: DMH7SIX)

• Drug Name: 5-Nitroindazole Drug Info
• Synonyms: 5-Nitro-1H-indazole; 5401-94-5; 1H-INDAZOLE, 5-NITRO-; UNII-235Y7P37ZD; CCRIS 4134; NSC 5032; EINECS 226-451-5; BRN 0007936; CHEMBL165372; WSGURAYTCUVDQL-UHFFFAOYSA-N; 235Y7P37ZD; MFCD00005693; 5NI; 2H-Indazole, 5-nitro-; 5-Nitroindazol; 5-nitro indazole; 5-nitro-indazole; 5-nitro-1H-indazol; 5-nitro-IH-indazole; 5-nitro-2H-indazole; PubChem15672; 4lm0; AC1L2IGS; ACMC-209lc9; DSSTox_RID_83391; DSSTox_CID_29272; 5-Nitroindazole, > DSSTox_GSID_49316; KSC490O7N; 5-Nitro-1H-indazole 99%; MLS000728712; 5-23-06-00180 (B

Indication

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

• Cross-matching ID:
  PubChem CID: 21501
  CAS Number: CAS 5401-94-5
  TTD Drug ID: DMH7SIX

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

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	[13]
L-NAME	DM01SR6	Hypertension	BA00-BA04	Phase 2	[14]
ACCLAIM	DM0FGDO	Angina pectoris	BA40	Phase 2	[15]
VAS-203	DMKU93J	Brain injury	NA07.Z	Phase 2	[16]
MTR105	DMT0K4F	Hypotension	BA20-BA21	Phase 2	[17]
Autologous cell based gene therapy	DMQA1VT	Pulmonary hypertension	BB01	Phase 1	[18]
L-NIL	DM6Y49D	N. A.	N. A.	Terminated	[19]
Acetate Ion	DMD08RH	Discovery agent	N.A.	Investigative	[1]
2-Methyl-2,4-Pentanediol	DMD45CU	Discovery agent	N.A.	Investigative	[1]
Heme	DMGC287	Discovery agent	N.A.	Investigative	[20]

Drug(s) Affected By Amine oxidase B (MAOB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[21]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[22]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[23]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[24]
Selegiline	DM6034S	Major depressive disorder	6A70.3	Approved	[25]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[26]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[27]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[28]
BENZYL BENZOATE	DMDPYI5	Infestations of lice and scabies	1G00.Z	Approved	[29]
Linezolid	DMGFPU2	Bacteremia	1A73	Approved	[30]

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	[1]
Nitric-oxide synthase inducible (NOS2)	TTF10I9	NOS2_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Amine oxidase B (MAOB)	OTTDFM1O	AOFB_HUMAN	Gene/Protein Processing	[2]

References

• [1] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [2] Inhibition of the bioactivation of the neurotoxin MPTP by antioxidants, redox agents and monoamine oxidase inhibitors. Food Chem Toxicol. 2011 Aug;49(8):1773-81.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury. Kidney Int. 2003 Mar;63(3):853-65.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] WO patent application no. 2014,0214,08, Method for treating cancer by anticancer agent co-administration.
• [12] Critical role of L-arginine in endothelial cell survival during oxidative stress. Circulation. 2003 May 27;107(20):2607-14.
• [13] 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.
• [14] 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.
• [15] CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Discovery of a series of aminopiperidines as novel iNOS inhibitors. Bioorg Med Chem Lett. 2008 Jan 1;18(1):336-43.
• [20] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [21] Inhibition potential of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites on the in vitro monoamine oxidase (MAO)-catalyzed deamination of the neurotransmitters serotonin and dopamine. Toxicol Lett. 2016 Jan 22;243:48-55.
• [22] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [23] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [24] Molecular Insights into Human Monoamine Oxidase B Inhibition by the Glitazone Anti-Diabetes Drugs. ACS Med Chem Lett. 2011 Oct 15;3(1):39-42.
• [25] Chromone, a privileged scaffold for the development of monoamine oxidase inhibitors. J Med Chem. 2011 Jul 28;54(14):5165-73.
• [26] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [27] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [28] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [29] Combining initro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. Chem Biol Interact. 2016 Jul 25;254:135-45.
• [30] Nonclinical Evaluation of Antibacterial Oxazolidinones Contezolid and Contezolid Acefosamil with Low Serotonergic Neurotoxicity. Chem Res Toxicol. 2021 May 17;34(5):1348-1354. doi: 10.1021/acs.chemrestox.0c00524. Epub 2021 Apr 29.