Details of the Drug Combination

General Information of Drug Combination (ID: DCSWHYJ)

Drug Combination Name
Mefloquine Guanfacine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Mefloquine   DMWT905 Guanfacine   DMPN5IH
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: 4.73
Bliss Independence Score: 4.73
Loewe Additivity Score: 5.57
LHighest Single Agent (HSA) Score: 5.57

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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 [8]
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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 [9]
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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 [10]
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Indication(s) of Guanfacine
Disease Entry ICD 11 Status REF
Attention deficit hyperactivity disorder 6A05.Z Approved [6]
Alzheimer disease 8A20 Phase 3 [7]
Guanfacine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor alpha-2A (ADRA2A) TTWG9A4 ADA2A_HUMAN Agonist [11]
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Guanfacine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [12]
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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 Guanfacine FDA Label
7 ClinicalTrials.gov (NCT03116126) Randomised Clinical Trial of Noradrenergic Add-on Therapy With Extended-Release Guanfacine in Alzheimer's Disease. U.S.National Institutes of Health.
8 An ultrastructural study of the effects of mefloquine on malaria parasites. Am J Trop Med Hyg. 1987 Jan;36(1):9-14.
9 Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33.
10 Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers. J Pharm Pharmacol. 2000 Oct;52(10):1265-9.
11 Scientific rationale for the use of alpha2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders. Mol Psychiatry. 2023 Apr 7:1-13.
12 An in vitro evaluation of guanfacine as a substrate for P-glycoprotein. Neuropsychiatr Dis Treat. 2011;7:501-5.