Details of the Drug Combination

General Information of Drug Combination (ID: DC6UP7U)

Drug Combination Name
NARINGENIN Mefloquine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs NARINGENIN   DMHAZLM Mefloquine   DMWT905
Small molecular drug 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: 2.89
Bliss Independence Score: 2.89
Loewe Additivity Score: 3.91
LHighest Single Agent (HSA) Score: 3.92

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
NARINGENIN Interacts with 5 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aromatase (CYP19A1) TTSZLWK CP19A_HUMAN Inhibitor [6]
Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1) TTIWB6L DHB1_HUMAN Inhibitor [7]
Estrogen receptor beta (ESR2) TTOM3J0 ESR2_HUMAN Inhibitor [8]
Lactoylglutathione lyase (GLO1) TTV9A7R LGUL_HUMAN Inhibitor [9]
Cytochrome P450 1B1 (CYP1B1) TTI84H7 CP1B1_HUMAN Inhibitor [10]
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NARINGENIN Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]
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NARINGENIN Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 105D7 (cyp105) DECV2ME CYP28_STRAW Metabolism [12]
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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 [13]
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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 [14]
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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 [15]
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References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
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 Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg Med Chem Lett. 2010 May 15;20(10):3050-64.
7 Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries. J Med Chem. 2008 Jul 24;51(14):4188-99.
8 Subtle side-chain modifications of the hop phytoestrogen 8-prenylnaringenin result in distinct agonist/antagonist activity profiles for estrogen re... J Med Chem. 2006 Dec 14;49(25):7357-65.
9 Structure-activity relationship of human GLO I inhibitory natural flavonoids and their growth inhibitory effects. Bioorg Med Chem. 2008 Apr 1;16(7):3969-75.
10 Selective inhibition of methoxyflavonoids on human CYP1B1 activity. Bioorg Med Chem. 2010 Sep 1;18(17):6310-5.
11 Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med. 2004 Mar 1;36(5):592-604.
12 The metagenome of Caracolus marginella gut microbiome using culture independent approaches and shotgun sequencing. Data Brief. 2017 Nov 22;16:501-505.
13 An ultrastructural study of the effects of mefloquine on malaria parasites. Am J Trop Med Hyg. 1987 Jan;36(1):9-14.
14 Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
15 Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers. J Pharm Pharmacol. 2000 Oct;52(10):1265-9.