General Information of Drug Combination (ID: DCJMECB)

Drug Combination Name
Lapatinib Mepacrine
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Lapatinib   DM3BH1Y Mepacrine   DMU8L7C
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: OVCAR3
Zero Interaction Potency (ZIP) Score: 0.74
Bliss Independence Score: 4
Loewe Additivity Score: 4.43
LHighest Single Agent (HSA) Score: 4.83

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Lapatinib
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [2]
Gastroesophageal junction adenocarcinoma 2B71 Approved [3]
Melanoma 2C30 Approved [3]
Lapatinib Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Erbb2 tyrosine kinase receptor (HER2) TT6EO5L ERBB2_HUMAN Inhibitor [6]
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [6]
Eukaryotic elongation factor 2 kinase (eEF-2K) TT1QFLA EF2K_HUMAN Inhibitor [7]
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Lapatinib Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [9]
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Lapatinib Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [11]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [10]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [11]
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Lapatinib Interacts with 36 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Decreases Activity [12]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [13]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [14]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [14]
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Increases Expression [14]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Activity [14]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [15]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Activity [12]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [16]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [17]
DNA topoisomerase 1 (TOP1) OT51O0CF TOP1_HUMAN Decreases Expression [18]
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Decreases Expression [18]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [18]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [16]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [19]
Receptor tyrosine-protein kinase erbB-3 (ERBB3) OTRSST0A ERBB3_HUMAN Decreases Activity [20]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [21]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [12]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Activity [16]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Activity [16]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Activity [12]
DNA replication licensing factor MCM7 (MCM7) OT6FXC6K MCM7_HUMAN Decreases Expression [16]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [18]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [12]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [18]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [18]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [17]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [22]
GTPase KRas (KRAS) OT78QCN8 RASK_HUMAN Decreases Response To Substance [23]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1) OTC6GISG DQA1_HUMAN Increases ADR [24]
Zinc finger protein SNAI1 (SNAI1) OTDPYAMC SNAI1_HUMAN Decreases Response To Substance [25]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Metabolism [18]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Increases Metabolism [18]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Response To Substance [25]
Tenascin-X (TNXB) OTVBWAV5 TENX_HUMAN Increases ADR [24]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1) OTVVI3UI DQB1_HUMAN Increases ADR [24]
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⏷ Show the Full List of 36 DOT(s)
Indication(s) of Mepacrine
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [4]
Mepacrine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Phospholipase A2 (PLA2G1B) TT9V5JH PA21B_HUMAN Inhibitor [4]
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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 [26]
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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 [27]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [27]
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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 [28]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Activity [29]
Zinc finger protein GLI1 (GLI1) OT1BTAJO GLI1_HUMAN Decreases Expression [28]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [30]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) OTSBQR6D PLCG1_HUMAN Decreases Phosphorylation [31]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [28]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [30]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [30]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [28]
Vascular endothelial growth factor receptor 2 (KDR) OT15797V VGFR2_HUMAN Decreases Phosphorylation [31]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Decreases Expression [32]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [28]
Casein kinase I isoform alpha (CSNK1A1) OTJ6O1IC KC1A_HUMAN Increases Expression [28]
Glycogen synthase kinase-3 beta (GSK3B) OTL3L14B GSK3B_HUMAN Increases Expression [28]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Cleavage [30]
Focal adhesion kinase 1 (PTK2) OT3Q1JDY FAK1_HUMAN Decreases Phosphorylation [31]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [30]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [33]
Forkhead box protein P3 (FOXP3) OTA9Z9OC FOXP3_HUMAN Increases Expression [30]
F-box/WD repeat-containing protein 1A (BTRC) OT2EZDGR FBW1A_HUMAN Decreases Expression [30]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Metabolism [27]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Transport [27]
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⏷ Show the Full List of 22 DOT(s)

References

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14 P450 3A-catalyzed O-dealkylation of lapatinib induces mitochondrial stress and activates Nrf2. Chem Res Toxicol. 2016 May 16;29(5):784-96.
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19 Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.
20 Suppression of HER2/HER3-mediated growth of breast cancer cells with combinations of GDC-0941 PI3K inhibitor, trastuzumab, and pertuzumab. Clin Cancer Res. 2009 Jun 15;15(12):4147-56. doi: 10.1158/1078-0432.CCR-08-2814. Epub 2009 Jun 9.
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