General Information of Drug Combination (ID: DCPEQC0)

Drug Combination Name
Amiloride Methylene blue
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Amiloride   DMRTSGP 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: 0.67
Bliss Independence Score: 0.67
Loewe Additivity Score: 1.5
LHighest Single Agent (HSA) Score: 1.5

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Amiloride
Disease Entry ICD 11 Status REF
Congestive heart failure BD10 Approved [2]
Edema MG29 Approved [3]
Amiloride Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Acid-sensing ion channel 1 (ASIC1) TTRJYB6 ASIC1_HUMAN Modulator [7]
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Amiloride Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Organic cation transporter 2 (SLC22A2) DT9IDPW S22A2_HUMAN Substrate [8]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [9]
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Amiloride Interacts with 15 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Diamine oxidase (AOC1) OTRC220K AOC1_HUMAN Decreases Activity [10]
3-phosphoinositide-dependent protein kinase 1 (PDPK1) OTT09ZVP PDPK1_HUMAN Decreases Phosphorylation [11]
Dysferlin (DYSF) OTNSKJU0 DYSF_HUMAN Decreases Expression [12]
Urokinase-type plasminogen activator (PLAU) OTX0QGKK UROK_HUMAN Decreases Activity [13]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Increases Expression [14]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Increases Expression [15]
Receptor tyrosine-protein kinase erbB-2 (ERBB2) OTOAUNCK ERBB2_HUMAN Decreases Phosphorylation [11]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Decreases Activity [16]
Myogenic factor 5 (MYF5) OTTVO2S5 MYF5_HUMAN Increases Expression [12]
G2/mitotic-specific cyclin-B1 (CCNB1) OT19S7E5 CCNB1_HUMAN Decreases Expression [17]
Pancreas/duodenum homeobox protein 1 (PDX1) OTX1DKRA PDX1_HUMAN Decreases Uptake [18]
Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PPP1CA) OT7Y43A1 PP1A_HUMAN Decreases Phosphorylation [11]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [16]
Multidrug and toxin extrusion protein 1 (SLC47A1) OTZX0U5Q S47A1_HUMAN Decreases Activity [19]
Glutamate receptor-interacting protein 1 (GRIP1) OT958HK1 GRIP1_HUMAN Affects Response To Substance [20]
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⏷ Show the Full List of 15 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 . [21]
Guanylate cyclase (GC) TT6HPVC NOUNIPROTAC Inhibitor [22]
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Methylene blue Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Amine oxidase B (MAOB) OTTDFM1O AOFB_HUMAN Decreases Activity [23]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [24]
Microtubule-associated protein tau (MAPT) OTMTP2Z7 TAU_HUMAN Increases Expression [25]
Glucose-6-phosphate 1-dehydrogenase (G6PD) OT300SMK G6PD_HUMAN Increases Activity [26]
Acetylcholinesterase (ACHE) OT2H8HG6 ACES_HUMAN Decreases Activity [27]
6-phosphogluconate dehydrogenase, decarboxylating (PGD) OTVG296F 6PGD_HUMAN Increases Activity [26]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases ADR [28]
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⏷ Show the Full List of 7 DOT(s)

References

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2 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: 2421).
3 Amiloride FDA Label
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 Reduction of intracellular pH inhibits the expression of VEGF in K562 cells after targeted inhibition of the Na+/H+ exchanger. Leuk Res. 2007 Apr;31(4):507-14. doi: 10.1016/j.leukres.2006.06.015. Epub 2006 Aug 1.
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
8 Characterization of regulatory mechanisms and states of human organic cation transporter 2. Am J Physiol Cell Physiol. 2006 Jun;290(6):C1521-31.
9 Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
10 Diamine oxidase is the amiloride-binding protein and is inhibited by amiloride analogues. J Biol Chem. 1994 Apr 1;269(13):9921-5.
11 Role of HER-2/neu signaling in sensitivity to tumor necrosis factor-related apoptosis-inducing ligand: enhancement of TRAIL-mediated apoptosis by amiloride. J Cell Biochem. 2005 Oct 1;96(2):376-89. doi: 10.1002/jcb.20512.
12 In vivo and in vitro dysferlin expression in human muscle satellite cells. J Neuropathol Exp Neurol. 2004 Oct;63(10):1104-13. doi: 10.1093/jnen/63.10.1104.
13 Amplification of urokinase gene in prostate cancer. Cancer Res. 2001 Jul 15;61(14):5340-4.
14 Amiloride, spironolactone, and potassium chloride in thiazide-treated hypertensive patients. Clin Pharmacol Ther. 1980 Apr;27(4):533-43. doi: 10.1038/clpt.1980.75.
15 Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro. Toxicol Sci. 2003 Aug;74(2):260-70. doi: 10.1093/toxsci/kfg113. Epub 2003 May 2.
16 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
17 Reduction in the radiation-induced late S phase and G2 blocks in HL-60 cell populations by amiloride, an efficient inhibitor of the Na+/H+ transporter. Cancer Res. 1998 Feb 1;58(3):413-20.
18 PDX-1 protein is internalized by lipid raft-dependent macropinocytosis. Cell Transplant. 2005;14(9):637-45. doi: 10.3727/000000005783982648.
19 Molecular identification and functional characterization of rat multidrug and toxin extrusion type transporter 1 as an organic cation/H+ antiporter in the kidney. Drug Metab Dispos. 2006 Nov;34(11):1868-74. doi: 10.1124/dmd.106.010876. Epub 2006 Aug 23.
20 Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.
21 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.
22 Curcumin ameliorates high glucose-induced acute vascular endothelial dysfunction in rat thoracic aorta. Clin Exp Pharmacol Physiol. 2009 Dec;36(12):1177-82.
23 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.
24 Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
25 Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression. Mol Neurodegener. 2006 Jul 26;1:6. doi: 10.1186/1750-1326-1-6.
26 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.
27 Profiling the Tox21 Chemical Collection for Acetylcholinesterase Inhibition. Environ Health Perspect. 2021 Apr;129(4):47008. doi: 10.1289/EHP6993. Epub 2021 Apr 12.
28 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.