General Information of Drug Combination (ID: DCIQW6K)

Drug Combination Name
Amodiaquine Albendazole
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Amodiaquine   DME4RA8 Albendazole   DMYZ57N
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: 8.2
Bliss Independence Score: 8.2
Loewe Additivity Score: 19.82
LHighest Single Agent (HSA) Score: 19.84

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 [6]
------------------------------------------------------------------------------------
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 [7]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [8]
Cytochrome P450 1B1 (CYP1B1) DE9QHP6 CP1B1_HUMAN Metabolism [7]
Glutathione S-transferase mu-4 (GSTM4) DERQ52Z GSTM4_HUMAN Metabolism [9]
Cytochrome P450 102A1 (cyp102) DE4OGUF CPXB_BACMB Metabolism [10]
------------------------------------------------------------------------------------
Amodiaquine Interacts with 34 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Activity [11]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Response To Substance [12]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Decreases Activity [13]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Decreases Activity [13]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Decreases Activity [13]
Proepiregulin (EREG) OTRM4NQY EREG_HUMAN Increases Expression [14]
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Decreases Expression [14]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [15]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Affects Phosphorylation [16]
Cathepsin D (CTSD) OTQZ36F3 CATD_HUMAN Decreases Activity [16]
Procathepsin L (CTSL) OTYTUW29 CATL1_HUMAN Decreases Activity [16]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Decreases Activity [16]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Increases Expression [14]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [12]
Bone morphogenetic protein 6 (BMP6) OT9WN536 BMP6_HUMAN Increases Expression [14]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Affects Expression [16]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [14]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Affects Expression [16]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Cleavage [12]
Tumor necrosis factor-inducible gene 6 protein (TNFAIP6) OT1SLUZH TSG6_HUMAN Decreases Expression [14]
Transcription factor E2F1 (E2F1) OTLKYBBC E2F1_HUMAN Affects Expression [16]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [12]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [12]
PTB-containing, cubilin and LRP1-interacting protein (PID1) OT5YJ7FI PCLI1_HUMAN Increases Expression [14]
Cytochrome P450 2A6 (CYP2A6) OT52TWG3 CP2A6_HUMAN Increases Metabolism [12]
Cytochrome P450 2E1 (CYP2E1) OTHQ17JG CP2E1_HUMAN Increases Metabolism [12]
Myeloperoxidase (MPO) OTOOXLIN PERM_HUMAN Increases ADR [17]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Increases Metabolism [12]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Metabolism [9]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Increases Metabolism [12]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Increases Metabolism [12]
Cytochrome P450 2A13 (CYP2A13) OTVUDLT3 CP2AD_HUMAN Increases Metabolism [12]
Cytochrome P450 2C18 (CYP2C18) OTY687L9 CP2CI_HUMAN Increases Metabolism [12]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Increases Metabolism [9]
------------------------------------------------------------------------------------
⏷ Show the Full List of 34 DOT(s)
Indication(s) of Albendazole
Disease Entry ICD 11 Status REF
Echinococcus granulosus infectious disease N.A. Approved [4]
Helminth infection 1F90.0 Approved [4]
Worm infection 1F90.Z Approved [5]
Albendazole Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tubulin beta (TUBB) TTYFKSZ NOUNIPROTAC Binder [19]
------------------------------------------------------------------------------------
Albendazole Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [20]
------------------------------------------------------------------------------------
Albendazole Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [21]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [11]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [22]
------------------------------------------------------------------------------------
Albendazole Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Increases Expression [11]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Expression [11]
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Increases Secretion [23]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [24]
Interleukin-6 receptor subunit alpha (IL6R) OTCQL07Z IL6RA_HUMAN Increases Expression [18]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [18]
Microtubule-associated protein tau (MAPT) OTMTP2Z7 TAU_HUMAN Decreases Expression [25]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [18]
HLA class II histocompatibility antigen, DM beta chain (HLA-DMB) OT17HGXJ DMB_HUMAN Affects Expression [26]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Increases Activity [27]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [28]
------------------------------------------------------------------------------------
⏷ Show the Full List of 11 DOT(s)

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 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 Albendazole FDA Label
5 Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
6 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.
7 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.
8 Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: implications for malaria treatment in Africa. Clin Pharmacol Ther. 2007 Aug;82(2):197-203.
9 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.
10 The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 2007 Jul;25(7):289-98.
11 Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells. Eur J Clin Pharmacol. 2002 Nov;58(8):537-42.
12 Apoptosis contributes to the cytotoxicity induced by amodiaquine and its major metabolite N-desethylamodiaquine in hepatic cells. Toxicol In Vitro. 2020 Feb;62:104669. doi: 10.1016/j.tiv.2019.104669. Epub 2019 Oct 16.
13 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.
14 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.
15 High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter. Carcinogenesis. 2002 Jun;23(6):949-57. doi: 10.1093/carcin/23.6.949.
16 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.
17 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
18 Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents. Leuk Res. 2010 Jul;34(7):917-24. doi: 10.1016/j.leukres.2009.12.002. Epub 2010 Feb 8.
19 Flubendazole interferes with a wide spectrum of cell homeostatic mechanisms in Echinococcus granulosus protoscoleces. Parasitol Int. 2009 Sep;58(3):270-7.
20 The anthelminthic agent albendazole does not interact with p-glycoprotein. Drug Metab Dispos. 2002 Apr;30(4):365-9.
21 Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003 Sep;59(5-6):429-42.
22 Danazol inhibits cytochrome P450 2J2 activity in a substrate-independent manner. Drug Metab Dispos. 2015 Aug;43(8):1250-3.
23 Stimulation of pro-inflammatory responses by mebendazole in human monocytic THP-1 cells through an ERK signaling pathway. Arch Toxicol. 2011 Mar;85(3):199-207. doi: 10.1007/s00204-010-0584-y. Epub 2010 Sep 17.
24 Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
25 Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression. Mol Neurodegener. 2006 Jul 26;1:6. doi: 10.1186/1750-1326-1-6.
26 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
27 A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
28 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.