General Information of Drug Combination (ID: DCTBR5P)

Drug Combination Name
Lapatinib MK-1775
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Lapatinib   DM3BH1Y MK-1775   DM3WDZ5
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HT29
Zero Interaction Potency (ZIP) Score: 8.73
Bliss Independence Score: 12.68
Loewe Additivity Score: 7.21
LHighest Single Agent (HSA) Score: 14.3

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 [7]
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [7]
Eukaryotic elongation factor 2 kinase (eEF-2K) TT1QFLA EF2K_HUMAN Inhibitor [8]
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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 [9]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [10]
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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 [11]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [12]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [11]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [12]
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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 [13]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [14]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [15]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [15]
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Increases Expression [15]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Activity [15]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [16]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Activity [13]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [17]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [18]
DNA topoisomerase 1 (TOP1) OT51O0CF TOP1_HUMAN Decreases Expression [19]
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Decreases Expression [19]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [19]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [17]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [20]
Receptor tyrosine-protein kinase erbB-3 (ERBB3) OTRSST0A ERBB3_HUMAN Decreases Activity [21]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [22]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [13]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Activity [17]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Activity [17]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Activity [13]
DNA replication licensing factor MCM7 (MCM7) OT6FXC6K MCM7_HUMAN Decreases Expression [17]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [19]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [13]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [19]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [19]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [18]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [23]
GTPase KRas (KRAS) OT78QCN8 RASK_HUMAN Decreases Response To Substance [24]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1) OTC6GISG DQA1_HUMAN Increases ADR [25]
Zinc finger protein SNAI1 (SNAI1) OTDPYAMC SNAI1_HUMAN Decreases Response To Substance [26]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Metabolism [19]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Increases Metabolism [19]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Response To Substance [26]
Tenascin-X (TNXB) OTVBWAV5 TENX_HUMAN Increases ADR [25]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1) OTVVI3UI DQB1_HUMAN Increases ADR [25]
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⏷ Show the Full List of 36 DOT(s)
Indication(s) of MK-1775
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 2 [4]
Solid tumour/cancer 2A00-2F9Z Phase 1 [5]
MK-1775 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Wee1-like protein kinase (WEE1) TTJFOAL WEE1_HUMAN Inhibitor [28]
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MK-1775 Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Phosphorylation [27]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Response To Substance [27]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Breast and ovarian cancer syndrome DC1B2O2 UWB1289+BRCA1 Investigative [29]
Breast carcinoma DCG942Q KPL1 Investigative [29]
Breast carcinoma DCBE7MQ OCUBM Investigative [29]
Carcinoma DCV0LXB EFM192B Investigative [29]
Carcinoma DCWF90P MDAMB436 Investigative [29]
Colon adenocarcinoma DCXJ4B4 LOVO Investigative [29]
Colon carcinoma DCDQG8R RKO Investigative [29]
Rectal adenocarcinoma DCVG4BJ SW837 Investigative [29]
Adenocarcinoma DCWQWWZ CAOV3 Investigative [1]
Adenocarcinoma DCHK8J8 A427 Investigative [1]
Adenocarcinoma DC1ZD85 NCIH2122 Investigative [1]
Adenocarcinoma DCEILRL NCIH520 Investigative [1]
Adenocarcinoma DC2QLEZ COLO320DM Investigative [1]
Adenocarcinoma DCY0VCX DLD1 Investigative [1]
Adenocarcinoma DCHSU4T HCT116 Investigative [1]
Amelanotic melanoma DC21Q7Q A2058 Investigative [1]
Ewing sarcoma-peripheral primitive neuroectodermal tumour DCRLKOF ES2 Investigative [1]
Germ cell tumour DCQ06O0 PA1 Investigative [1]
Malignant melanoma DCDY7WK A375 Investigative [1]
Malignant melanoma DCGE571 HT144 Investigative [1]
Malignant melanoma DCQJQ3Q RPMI7951 Investigative [1]
Malignant melanoma DCUDG1U SKMEL30 Investigative [1]
Malignant melanoma DC79KEQ UACC62 Investigative [1]
Mesothelioma DCYTAS1 MSTO Investigative [1]
Non small cell carcinoma DCFHHSE SKMES1 Investigative [1]
Ovarian endometrioid adenocarcinoma DCQ4R64 A2780 Investigative [1]
Prostate carcinoma DCDIBWQ VCAP Investigative [1]
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⏷ Show the Full List of 27 DrugCom(s)

References

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3 Lapatinib FDA Label
4 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: 7702).
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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7 Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
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9 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
10 The role of efflux and uptake transporters in [N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine (GW572016, lapatinib) disposition and drug interactions. Drug Metab Dispos. 2008 Apr;36(4):695-701.
11 Mechanism-based inactivation of cytochrome P450 3A4 by lapatinib. Mol Pharmacol. 2010 Oct;78(4):693-703.
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13 The dual ErbB1/ErbB2 inhibitor, lapatinib (GW572016), cooperates with tamoxifen to inhibit both cell proliferation- and estrogen-dependent gene expression in antiestrogen-resistant breast cancer. Cancer Res. 2005 Jan 1;65(1):18-25.
14 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
15 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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17 CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models. Genes Cancer. 2014 Jul;5(7-8):261-72. doi: 10.18632/genesandcancer.24.
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21 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.
22 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
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