Details of the Drug Combination

General Information of Drug Combination (ID: DCON1MF)

Drug Combination Name
Hydralazine Methylene blue
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Hydralazine   DMU8JGH Methylene blue   DMJAPE7
Small molecular drug N.A.
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 4.81
Bliss Independence Score: 4.81
Loewe Additivity Score: 5.61
LHighest Single Agent (HSA) Score: 5.61

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Hydralazine
Disease Entry ICD 11 Status REF
Chronic heart failure BD1Z Approved [2]
Hypertension BA00-BA04 Approved [3]
Malignant essential hypertension BA00 Approved [2]
Hydralazine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Membrane copper amine oxidase (AOC3) TT7HC21 AOC3_HUMAN Modulator [6]
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Hydralazine Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
RNA cytidine acetyltransferase (hALP) DEZV4AP NAT10_HUMAN Metabolism [7]
N-acetyltransferase 1 (NAT1) DE7OAB3 ARY1_HUMAN Metabolism [8]
N-acetyltransferase 2 (NAT2) DER7TA0 ARY2_HUMAN Metabolism [8]
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Hydralazine Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Arylamine N-acetyltransferase 2 (NAT2) OTBPDQOY ARY2_HUMAN Increases Acetylation [9]
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Increases Expression [10]
Adenomatous polyposis coli protein (APC) OTKV0TIK APC_HUMAN Decreases Methylation [10]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Methylation [10]
Bis(5'-adenosyl)-triphosphatase (FHIT) OTGWBSLA FHIT_HUMAN Increases Expression [10]
Death-associated protein kinase 1 (DAPK1) OTNCNUCO DAPK1_HUMAN Increases Expression [10]
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [11]
Collagen alpha-1(I) chain (COL1A1) OTI31178 CO1A1_HUMAN Decreases Expression [12]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [13]
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⏷ Show the Full List of 9 DOT(s)
Indication(s) of Methylene blue
Disease Entry ICD 11 Status REF
Acquired methemoglobinemia 3A93 Approved [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [5]
Methylene blue Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Monoamine oxidase (MAO) TT32XQJ NOUNIPROTAC . [14]
Guanylate cyclase (GC) TT6HPVC NOUNIPROTAC Inhibitor [15]
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Methylene blue Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
6-phosphogluconate dehydrogenase, decarboxylating (PGD) OTVG296F 6PGD_HUMAN Increases Activity [16]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Hydralazine FDA Label
3 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: 7326).
4 Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue. FEBS Lett. 1998 Feb 6;422(3):311-4.
5 ClinicalTrials.gov (NCT04370288) Clinical Application of Methylene Blue for Treatment of Covid-19 Patients. U.S. National Institutes of Health.
6 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
7 Prizidilol, an antihypertensive with precapillary vasodilator and beta-adrenoceptor blocking actions, in primary hypertension. Clin Pharmacol Ther. 1981 May;29(5):588-93.
8 N-acetyltransferase 2 genotype-dependent N-acetylation of hydralazine in human hepatocytes. Drug Metab Dispos. 2017 Dec;45(12):1276-1281.
9 Eukaryotic arylamine N-acetyltransferase. Investigation of substrate specificity by high-throughput screening. Biochem Pharmacol. 2005 Jan 15;69(2):347-59. doi: 10.1016/j.bcp.2004.09.014. Epub 2004 Nov 24.
10 A phase I study of hydralazine to demethylate and reactivate the expression of tumor suppressor genes. BMC Cancer. 2005 Apr 29;5:44.
11 Sympathetic activity in idiopathic dilated cardiomyopathy. Influence of captopril and hydralazine. Cardiovasc Drugs Ther. 1987 Aug;1(2):177-81. doi: 10.1007/BF02125471.
12 Hydralazine inhibits human peritoneal mesothelial cell proliferation and collagen synthesis. Nephrol Dial Transplant. 1996 Nov;11(11):2276-81. doi: 10.1093/oxfordjournals.ndt.a027148.
13 Albumin Protects Lung Cells against Acrolein Cytotoxicity and Acrolein-Adducted Albumin Increases Heme Oxygenase 1 Transcripts. Chem Res Toxicol. 2020 Jul 20;33(7):1969-1979. doi: 10.1021/acs.chemrestox.0c00146. Epub 2020 Jun 29.
14 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.
15 Curcumin ameliorates high glucose-induced acute vascular endothelial dysfunction in rat thoracic aorta. Clin Exp Pharmacol Physiol. 2009 Dec;36(12):1177-82.
16 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.