General Information of Drug Combination (ID: DCN3RCX)

Drug Combination Name
Dexrazoxane Mepacrine
Indication
Disease Entry Status REF
Colon carcinoma Investigative [1]
Component Drugs Dexrazoxane   DMD7X1O Mepacrine   DMU8L7C
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KM12
Zero Interaction Potency (ZIP) Score: 13.9
Bliss Independence Score: 13.21
Loewe Additivity Score: 12.78
LHighest Single Agent (HSA) Score: 17.13

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Dexrazoxane
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [2]
Chemoprotection N.A. Approved [3]
Inflammatory breast cancer 2C62 Approved [4]
Respiratory tract disease CB7Z Investigative [5]
Dexrazoxane Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II beta (TOP2B) TT4NVEM TOP2B_HUMAN Inhibitor [7]
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Modulator [8]
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Dexrazoxane Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Dihydropyrimidinase-related protein 1 (DRP1) DE0EUXB DPYL1_HUMAN Metabolism [9]
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Dexrazoxane Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Decreases Activity [10]
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Indication(s) of Mepacrine
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [6]
Mepacrine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Phospholipase A2 (PLA2G1B) TT9V5JH PA21B_HUMAN Inhibitor [6]
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Mepacrine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [11]
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Mepacrine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [12]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [12]
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Mepacrine Interacts with 22 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [13]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [14]
Zinc finger protein GLI1 (GLI1) OT1BTAJO GLI1_HUMAN Decreases Expression [13]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [15]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) OTSBQR6D PLCG1_HUMAN Decreases Phosphorylation [16]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [13]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [15]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [15]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [13]
Vascular endothelial growth factor receptor 2 (KDR) OT15797V VGFR2_HUMAN Decreases Phosphorylation [16]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Decreases Expression [17]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [13]
Casein kinase I isoform alpha (CSNK1A1) OTJ6O1IC KC1A_HUMAN Increases Expression [13]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Expression [13]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [15]
Focal adhesion kinase 1 (PTK2) OT3Q1JDY FAK1_HUMAN Decreases Phosphorylation [16]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [15]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [18]
Forkhead box protein P3 (FOXP3) OTA9Z9OC FOXP3_HUMAN Increases Expression [15]
F-box/WD repeat-containing protein 1A (BTRC) OT2EZDGR FBW1A_HUMAN Decreases Expression [15]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Metabolism [12]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Transport [12]
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⏷ Show the Full List of 22 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Papillary renal cell carcinoma DCPHWFA ACHN Investigative [19]
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References

1 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
2 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: 7330).
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Dexrazoxane FDA Label
5 Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.
6 Involvement of protein kinase C activation in L-leucine-induced stimulation of protein synthesis in l6 myotubes. Cytotechnology. 2003 Nov;43(1-3):97-103.
7 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9 Metabolism of the cardioprotective drug dexrazoxane and one of its metabolites by isolated rat myocytes, hepatocytes, and blood. Drug Metab Dispos. 2005 Jun;33(6):719-25.
10 Investigation of novel dexrazoxane analogue JR-311 shows significant cardioprotective effects through topoisomerase IIbeta but not its iron chelating metabolite. Toxicology. 2017 Dec 1;392:1-10. doi: 10.1016/j.tox.2017.09.012. Epub 2017 Sep 21.
11 Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem J. 2005 Jan 15;385(Pt 2):419-26.
12 Quinacrine is mainly metabolized to mono-desethyl quinacrine by CYP3A4/5 and its brain accumulation is limited by P-glycoprotein. Drug Metab Dispos. 2006 Jul;34(7):1136-44.
13 Nanoquinacrine caused apoptosis in oral cancer stem cells by disrupting the interaction between GLI1 and catenin through activation of GSK3. Toxicol Appl Pharmacol. 2017 Sep 1;330:53-64. doi: 10.1016/j.taap.2017.07.008. Epub 2017 Jul 15.
14 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.
15 Quinacrine induces the apoptosis of human leukemia U937 cells through FOXP3/miR-183/-TrCP/SP1 axis-mediated BAX upregulation. Toxicol Appl Pharmacol. 2017 Nov 1;334:35-46. doi: 10.1016/j.taap.2017.08.019. Epub 2017 Sep 1.
16 Quinacrine is active in preclinical models of glioblastoma through suppressing angiogenesis, inducing oxidative stress and activating AMPK. Toxicol In Vitro. 2022 Sep;83:105420. doi: 10.1016/j.tiv.2022.105420. Epub 2022 Jun 17.
17 Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and highlights mechanisms of action. Arch Toxicol. 2021 Jan;95(1):321-336. doi: 10.1007/s00204-020-02902-3. Epub 2020 Sep 10.
18 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
19 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.