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

General Information of Drug (ID: DMJAPE7)

• Drug Name: Methylene blue Drug Info
• Synonyms: methylene blue; 61-73-4; Methylthioninium chloride; Swiss Blue; Chromosmon; Methylene Blue N; Methylenium ceruleum; Urolene blue; Methylene Blue chloride; Solvent blue 8; Bleu de methylene; Methylene Blue G; Methylene Blue A; External Blue 1; Methylene Blue D; Methylene Blue B; Methylene Blue anhydrous; CI Basic Blue 9; Methylene Blue ZF; Methylene Blue SP; Methylene Blue NZ; Methylene Blue BX; Methylene Blue BD; Methylene Blue SG; Tetramethylene Blue; Methylene Blue ZX; Methylene Blue FZ; Methylene Blue BP; Calcozine; 3,7-Bis-dimethylamino-phenothiazin-5-ylium

Indication

Disease Entry	ICD 11	Status	REF
Acquired methemoglobinemia	3A93	Approved	[1]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[2]

• Cross-matching ID:
  PubChem CID: 6099
  ChEBI ID: CHEMBL405110
  CAS Number: CAS 61-73-4
  TTD Drug ID: DMJAPE7

Molecule-Related Drug Atlas

Drug(s) Targeting Monoamine oxidase (MAO)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Moclobemide	DMNZWL7	Depression	6A70-6A7Z	Approved	[6]
Phenelzine	DMHIDUE	Depression	6A70-6A7Z	Approved	[6]
Tranylcypromine	DMGB5RE	Major depressive disorder	6A70.3	Approved	[6]
Selegiline	DM6034S	Major depressive disorder	6A70.3	Approved	[6]
Clorgyline	DMCEUJD	Parkinson disease	8A00.0	Approved	[6]
Pargyline	DMM0HR1	Hypertension	BA00-BA04	Approved	[6]
Ergoloid mesylate	DMORPBA	Alzheimer disease	8A20	Approved	[7]
Cyclopropylamine derivative 11	DMMJ0YN	N. A.	N. A.	Patented	[8]
PMID27019002-Compound-20a	DMRX748	N. A.	N. A.	Patented	[8]
Cyclopropylamine derivative 9	DMX7YAL	N. A.	N. A.	Patented	[8]

Drug(s) Targeting Guanylate cyclase (GC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[9]
Isosorbide Dinitrate	DMBI4JG	Anal fissure	DB50.0	Approved	[9]
Isosorbide Mononitrate	DMYLMU0	Angina pectoris	BA40	Approved	[9]
Erythrityl Tetranitrate	DMFGQ2S	Angina pectoris	BA40	Approved	[9]
Pirsidomine	DMHI6GE	Angina pectoris	BA40	Phase 2	[10]
IW-1701	DM457XO	Sickle-cell disorder	3A51	Phase 2	[11]

Drug(s) Affected By 6-phosphogluconate dehydrogenase, decarboxylating (PGD)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[12]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[13]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[14]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[16]
Disulfiram	DMCL2OK	Alcohol dependence	6C40.2	Approved	[17]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[18]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[19]
Benzoic Acid	DMKB9FI	Alopecia areata	ED70.2	Approved	[17]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Guanylate cyclase (GC)	TT6HPVC	NOUNIPROTAC	Inhibitor	[3]
Monoamine oxidase (MAO)	TT32XQJ	NOUNIPROTAC	Not Available	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
6-phosphogluconate dehydrogenase, decarboxylating (PGD)	OTVG296F	6PGD_HUMAN	Gene/Protein Processing	[5]

References

• [1] Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue. FEBS Lett. 1998 Feb 6;422(3):311-4.
• [2] ClinicalTrials.gov (NCT04370288) Clinical Application of Methylene Blue for Treatment of Covid-19 Patients. U.S. National Institutes of Health.
• [3] Curcumin ameliorates high glucose-induced acute vascular endothelial dysfunction in rat thoracic aorta. Clin Exp Pharmacol Physiol. 2009 Dec;36(12):1177-82.
• [4] Photoluminescence of CdTe nanocrystals modulated by methylene blue and DNA. A label-free luminescent signaling nanohybrid platform. Phys Chem Chem Phys. 2009 Jul 7;11(25):5062-9.
• [5] Defenses against oxidation in human erythrocytes: role of glutathione reductase in the activation of glucose decarboxylation by hemolytic drugs. J Lab Clin Med. 1991 Apr;117(4):325-31.
• [6] Novel monoamine oxidase inhibitors: a patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):91-110.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] LSD1 inhibitors: a patent review (2010-2015).Expert Opin Ther Pat. 2016 May;26(5):565-80.
• [9] Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart. Mol Cell Biochem. 2010 Jan;333(1-2):191-201.
• [10] Activation of soluble guanylyl cyclase by the nitrovasodilator 3-morpholinosydnonimine involves formation of S-nitrosoglutathione. Mol Pharmacol. 1998 Jul;54(1):207-12.
• [11] Clinical pipeline report, company report or official report of Cyclerion Therapeutics.
• [12] 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.
• [13] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [14] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [15] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [16] 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.
• [17] Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds. Toxicol Sci. 2010 Sep;117(1):81-9.
• [18] 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.
• [19] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [20] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.