Details of the Drug Combination

General Information of Drug Combination (ID: DC7PHFF)

Drug Combination Name
Omacetaxine mepesuccinate Mefloquine
Indication
Disease Entry Status REF
DD2 Investigative [1]
Component Drugs Omacetaxine mepesuccinate   DMPU2WX Mefloquine   DMWT905
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DD2
Zero Interaction Potency (ZIP) Score: 13.084
Bliss Independence Score: 14.235
Loewe Additivity Score: 8.46
LHighest Single Agent (HSA) Score: 14.469

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Omacetaxine mepesuccinate
Disease Entry ICD 11 Status REF
Adult acute monocytic leukemia N.A. Approved [2]
Chronic myelogenous leukaemia 2A20.0 Approved [2]
Chronic myeloid leukaemia 2A20 Approved [3]
Leukemia N.A. Approved [2]
Omacetaxine mepesuccinate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Ribosome A (hRA) TTA4FIU NOUNIPROTAC Modulator [8]
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Omacetaxine mepesuccinate Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Inhibitor of nuclear factor kappa-B kinase subunit alpha (CHUK) OTLF4ZB1 IKKA_HUMAN Increases Phosphorylation [9]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [10]
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) OTTOMI8J PK3CA_HUMAN Decreases Expression [10]
Neurogenic locus notch homolog protein 1 (NOTCH1) OTI1WADQ NOTC1_HUMAN Increases Expression [9]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Increases Expression [10]
Nuclear factor NF-kappa-B p100 subunit (NFKB2) OTS231V7 NFKB2_HUMAN Increases Expression [9]
Transcription factor RelB (RELB) OTU3QYEF RELB_HUMAN Increases Expression [9]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Increases Expression [9]
Jouberin (AHI1) OT8K2YWY AHI1_HUMAN Increases Expression [11]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Increases Expression [10]
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⏷ Show the Full List of 11 DOT(s)
Indication(s) of Mefloquine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [5]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [6]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [6]
Progressive multifocal leukoencephalopathy 8A45.02 Investigative [7]
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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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Hepatoblastoma DCBQ31L HB3 Investigative [15]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Omacetaxine mepesuccinate 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: 7454).
4 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 019578
5 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.
6 Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
7 Mefloquine FDA Label
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
9 Synergistic killing effects of homoharringtonine and arsenic trioxide on acute myeloid leukemia stem cells and the underlying mechanisms. J Exp Clin Cancer Res. 2019 Jul 15;38(1):308. doi: 10.1186/s13046-019-1295-8.
10 Homoharringtonine suppresses LoVo cell growth by inhibiting EphB4 and the PI3K/AKT and MAPK/EKR1/2 signaling pathways. Food Chem Toxicol. 2020 Feb;136:110960. doi: 10.1016/j.fct.2019.110960. Epub 2019 Nov 11.
11 [Expression and function of Ahi-1 gene in Jurkat cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Apr;17(2):445-9.
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.
15 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976