Details of the Drug Combination

General Information of Drug Combination (ID: DCK9J2H)

Drug Combination Name
Amodiaquine Brincidofovir
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Amodiaquine   DME4RA8 Brincidofovir   DMS0PND
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 3.24
Bliss Independence Score: 3.24
Loewe Additivity Score: 4.21
LHighest Single Agent (HSA) Score: 4.21

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Amodiaquine
Disease Entry ICD 11 Status REF
Malaria 1F40-1F45 Approved [2]
Middle East Respiratory Syndrome (MERS) 1D64 Preclinical [3]
Severe acute respiratory syndrome (SARS) 1D65 Preclinical [3]
Amodiaquine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Histamine N-methyltransferase (HNMT) TT2B6EV HNMT_HUMAN Inhibitor [5]
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Amodiaquine Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [6]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [7]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [6]
Glutathione S-transferase mu-4 (GSTM4) DERQ52Z GSTM4_HUMAN Metabolism [8]
Cytochrome P450 102A1 (cyp102) DE4OGUF CPXB_BACMB Metabolism [9]
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Amodiaquine Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [10]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [11]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Affects Phosphorylation [12]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [11]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Affects Expression [12]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Decreases Expression [11]
Transcription factor E2F1 (E2F1) OTLKYBBC E2F1_HUMAN Affects Expression [12]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [11]
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⏷ Show the Full List of 8 DOT(s)
Indication(s) of Brincidofovir
Disease Entry ICD 11 Status REF
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [4]

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Drug information of Amodiaquine, 2008. eduDrugs.
3 Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
4 A rational roadmap for SARS-CoV-2/COVID-19 pharmacotherapeutic research and development: IUPHAR Review 29. Br J Pharmacol. 2020 May 1;10.1111/bph.15094.
5 Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on, Propionibacterium acnes and lipopolysaccharide-induced hepatitis in mice. Eur J Pharmacol. 2007 Mar 8;558(1-3):179-84.
6 Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate. J Pharmacol Exp Ther. 2002 Feb;300(2):399-407.
7 Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: implications for malaria treatment in Africa. Clin Pharmacol Ther. 2007 Aug;82(2):197-203.
8 Human glutathione S-transferases- and NAD(P)H:quinone oxidoreductase 1-catalyzed inactivation of reactive quinoneimines of amodiaquine and N-desethylamodiaquine: possible implications for susceptibility to amodiaquine-induced liver toxicity. Toxicol Lett. 2017 Jun 5;275:83-91.
9 The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 2007 Jul;25(7):289-98.
10 Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
11 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
12 The antimalarial amodiaquine causes autophagic-lysosomal and proliferative blockade sensitizing human melanoma cells to starvation- and chemotherapy-induced cell death. Autophagy. 2013 Dec;9(12):2087-102. doi: 10.4161/auto.26506. Epub 2013 Oct 8.