Details of the Drug Combination

General Information of Drug Combination (ID: DCJAU4N)

Drug Combination Name
Nitrosoglutathione Mefloquine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Nitrosoglutathione   DMZ9WI4 Mefloquine   DMWT905
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 4.98
Bliss Independence Score: 4.98
Loewe Additivity Score: 5.76
LHighest Single Agent (HSA) Score: 5.76

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Nitrosoglutathione Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
S-(hydroxymethyl)glutathione dehydrogenase (adh) DEAH3PE A0A0A7DS01_VIBCL Metabolism [6]
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Nitrosoglutathione Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Serine protease HTRA2, mitochondrial (HTRA2) OTC7616F HTRA2_HUMAN Affects Localization [7]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Decreases Secretion [8]
Interleukin-12 subunit beta (IL12B) OT0JF8A3 IL12B_HUMAN Decreases Expression [8]
Transcription factor Sp3 (SP3) OTYDQZ1T SP3_HUMAN Decreases Activity [9]
Carbonyl reductase 1 (CBR1) OTQ3A541 CBR1_HUMAN Increases Reduction [10]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Increases Response To Substance [11]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of Mefloquine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [3]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [4]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [4]
Progressive multifocal leukoencephalopathy 8A45.02 Investigative [5]
Mefloquine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Plasmodium 80S ribosome (Malaria 80S) TTT28H3 NOUNIPROTAC Binder [12]
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Mefloquine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [13]
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Mefloquine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [14]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 019578
3 ClinicalTrials.gov (NCT04347031) An Open Randomized Study of the Effectiveness of Mefloquine for the Treatment of Patients With COVID19. U.S. National Institutes of Health.
4 Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
5 Mefloquine FDA Label
6 Nitrosative stress response in Vibrio cholerae: role of S-nitrosoglutathione reductase. Appl Biochem Biotechnol. 2017 Jul;182(3):871-884.
7 The induction of reactive oxygen species and loss of mitochondrial Omi/HtrA2 is associated with S-nitrosoglutathione-induced apoptosis in human endothelial cells. Toxicol Appl Pharmacol. 2010 May 1;244(3):374-84. doi: 10.1016/j.taap.2010.02.004. Epub 2010 Feb 11.
8 Regulatory role of nitric oxide on monocyte-derived dendritic cell functions. J Interferon Cytokine Res. 2003 Aug;23(8):423-31. doi: 10.1089/107999003322277838.
9 Concentration-dependent effects of endogenous S-nitrosoglutathione on gene regulation by specificity proteins Sp3 and Sp1. Biochem J. 2004 May 15;380(Pt 1):67-74. doi: 10.1042/BJ20031687.
10 Studies on reduction of S-nitrosoglutathione by human carbonyl reductases 1 and 3. Chem Biol Interact. 2011 May 30;191(1-3):95-103.
11 Hypersensitivity of ataxia-telangiectasia fibroblasts to a nitric oxide donor. Free Radic Biol Med. 1997;22(1-2):343-7. doi: 10.1016/s0891-5849(96)00336-x.
12 An ultrastructural study of the effects of mefloquine on malaria parasites. Am J Trop Med Hyg. 1987 Jan;36(1):9-14.
13 Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
14 Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers. J Pharm Pharmacol. 2000 Oct;52(10):1265-9.