Details of the Drug Combination

General Information of Drug Combination (ID: DCEJ7BH)

Drug Combination Name
Lapatinib Capecitabine
Indication
Disease Entry Status REF
Breast Cancer Phase 1 [1]
Component Drugs Lapatinib   DM3BH1Y Capecitabine   DMTS85L
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

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 Capecitabine
Disease Entry ICD 11 Status REF
Adenocarcinoma 2D40 Approved [4]
Colon adenocarcinoma N.A. Approved [4]
Colorectal cancer 2B91.Z Approved [5]
Metastasis from malignant tumor of colon N.A. Approved [4]
Rectal adenocarcinoma 2B92 Approved [4]
Breast cancer 2C60-2C65 Phase 3 [5]
Colon cancer 2B90.Z Investigative [4]
Gastric cancer 2B72 Investigative [4]
Capecitabine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Candida Thymidylate synthase (Candi TMP1) TTU6BFZ TYSY_CANAL Inhibitor [29]
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Capecitabine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytidine aminohydrolase (CDA) DEKEDRC CDD_HUMAN Metabolism [30]
Thymidine phosphorylase (TYMP) DE4HCYL TYPH_HUMAN Metabolism [31]
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Capecitabine Interacts with 65 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Dihydropyrimidine dehydrogenase (DPYD) OTWRF2NR DPYD_HUMAN Increases Expression [32]
Prostaglandin G/H synthase 2 (PTGS2) OT75U9M4 PGH2_HUMAN Decreases Expression [33]
Cyclin-dependent kinase inhibitor 2A (CDKN2A) OTN0ZWAE CDN2A_HUMAN Decreases Expression [33]
C-C motif chemokine 21 (CCL21) OT7DOXEM CCL21_HUMAN Decreases Expression [27]
CCN family member 1 (CCN1) OTKJBEMD CCN1_HUMAN Decreases Expression [27]
Aquaporin-8 (AQP8) OT99JKME AQP8_HUMAN Increases Expression [27]
Complement C3 (C3) OTCH5GS0 CO3_HUMAN Decreases Expression [27]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1) OTC6GISG DQA1_HUMAN Decreases Expression [27]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Secretion [34]
B-lymphocyte antigen CD20 (MS4A1) OTZTVUBX CD20_HUMAN Decreases Expression [27]
Nuclear receptor subfamily 4immunitygroup A member 1 (NR4A1) OTGP6GA4 NR4A1_HUMAN Decreases Expression [27]
40-kDa huntingtin-associated protein (F8A1) OTXTQ59R HAP40_HUMAN Decreases Expression [27]
Chloride anion exchanger (SLC26A3) OTBNK2U2 S26A3_HUMAN Increases Expression [27]
Nuclear receptor subfamily 4 group A member 2 (NR4A2) OT3F9IR2 NR4A2_HUMAN Decreases Expression [27]
Potassium-transporting ATPase alpha chain 2 (ATP12A) OTSQSKEK AT12A_HUMAN Increases Expression [27]
Serine/threonine-protein kinase SIK1 (SIK1) OT6FCHME SIK1_HUMAN Decreases Expression [27]
Hemoglobin subunit beta (HBB) OT514IKQ HBB_HUMAN Decreases Expression [27]
Hemoglobin subunit alpha (HBA1) OTW2BQF4 HBA_HUMAN Decreases Expression [27]
Paired box protein Pax-5 (PAX5) OTYBJJWX PAX5_HUMAN Decreases Expression [27]
Endoplasmic reticulum aminopeptidase 2 (ERAP2) OTEMENYF ERAP2_HUMAN Decreases Expression [27]
Fc receptor-like A (FCRLA) OT6MK4M1 FCRLA_HUMAN Decreases Expression [27]
Leucine-rich repeat-containing protein 15 (LRRC15) OTX7JL8H LRC15_HUMAN Decreases Expression [27]
C-C motif chemokine 19 (CCL19) OTQ2UJMH CCL19_HUMAN Decreases Expression [27]
E3 ubiquitin-protein ligase TRIM31 (TRIM31) OT7VW6RP TRI31_HUMAN Increases Expression [27]
Interleukin-1 receptor type 2 (IL1R2) OT0G7E35 IL1R2_HUMAN Increases Response To Substance [28]
Interleukin-17 receptor B (IL17RB) OT0KDNSF I17RB_HUMAN Increases Response To Substance [28]
Glycogen phosphorylase, brain form (PYGB) OT2ZTJT0 PYGB_HUMAN Increases Response To Substance [28]
Calcium and integrin-binding protein 1 (CIB1) OT4BVCRU CIB1_HUMAN Increases Response To Substance [28]
1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2) OT5I4Y9K PLCB_HUMAN Increases Response To Substance [28]
cAMP-dependent protein kinase catalytic subunit beta (PRKACB) OT6RMDCE KAPCB_HUMAN Decreases Response To Substance [28]
Claudin-3 (CLDN3) OT71MN9S CLD3_HUMAN Increases Response To Substance [28]
Replication protein A 70 kDa DNA-binding subunit (RPA1) OT76POLP RFA1_HUMAN Decreases Response To Substance [28]
Protein flightless-1 homolog (FLII) OT7G9JG6 FLII_HUMAN Decreases Response To Substance [28]
Stress-induced-phosphoprotein 1 (STIP1) OT7TXLOX STIP1_HUMAN Decreases Response To Substance [28]
Ras-related protein R-Ras2 (RRAS2) OT83NCEB RRAS2_HUMAN Decreases Response To Substance [28]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Decreases Response To Substance [28]
Cocaine esterase (CES2) OTC647SQ EST2_HUMAN Increases Response To Substance [35]
Ras-related protein Rab-40B (RAB40B) OTCA9ZF5 RB40B_HUMAN Increases Response To Substance [28]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Increases Response To Substance [28]
Iron-sulfur clusters transporter ABCB7, mitochondrial (ABCB7) OTDNTHNR ABCB7_HUMAN Decreases Response To Substance [28]
Tyrosine-protein phosphatase non-receptor type 13 (PTPN13) OTESFZSO PTN13_HUMAN Decreases Response To Substance [28]
ADP-ribosylation factor-like protein 4D (ARL4D) OTG5I3KU ARL4D_HUMAN Decreases Response To Substance [28]
Double-strand break repair protein MRE11 (MRE11) OTGU8TZM MRE11_HUMAN Decreases Response To Substance [28]
Inorganic pyrophosphatase (PPA1) OTHZK1QB IPYR_HUMAN Increases Response To Substance [28]
Polycystin-2 (PKD2) OTIXBU8H PKD2_HUMAN Decreases Response To Substance [28]
Protein S100-P (S100P) OTJCXNJG S100P_HUMAN Increases Response To Substance [28]
Transcriptional activator Myb (MYB) OTJH64IV MYB_HUMAN Increases Response To Substance [28]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (PLCE1) OTJISZOX PLCE1_HUMAN Increases Response To Substance [28]
Plakophilin-2 (PKP2) OTJOVF68 PKP2_HUMAN Increases Response To Substance [28]
Transcriptional enhancer factor TEF-1 (TEAD1) OTK6971C TEAD1_HUMAN Decreases Response To Substance [28]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Decreases Response To Substance [28]
Myelin regulatory factor (MYRF) OTKF6AEB MYRF_HUMAN Increases Response To Substance [28]
Galectin-4 (LGALS4) OTKQCG0H LEG4_HUMAN Increases Response To Substance [28]
Four and a half LIM domains protein 1 (FHL1) OTN535SU FHL1_HUMAN Decreases Response To Substance [28]
Hepatoma-derived growth factor-related protein 3 (HDGFL3) OTNN7WYH HDGR3_HUMAN Decreases Response To Substance [28]
E3 ubiquitin-protein ligase TRIM15 (TRIM15) OTNYAKP6 TRI15_HUMAN Increases Response To Substance [28]
Dermatan-sulfate epimerase (DSE) OTQ108VJ DSE_HUMAN Decreases Response To Substance [28]
Anterior gradient protein 2 homolog (AGR2) OTRRZT7W AGR2_HUMAN Increases Response To Substance [28]
Receptor tyrosine-protein kinase erbB-3 (ERBB3) OTRSST0A ERBB3_HUMAN Increases Response To Substance [28]
Aldo-keto reductase family 1 member B1 (AKR1B1) OTRX72TH ALDR_HUMAN Decreases Response To Substance [28]
Aldo-keto reductase family 1 member C3 (AKR1C3) OTU2SXBA AK1C3_HUMAN Increases Response To Substance [28]
3-ketoacyl-CoA thiolase, peroxisomal (ACAA1) OTVKRET0 THIK_HUMAN Increases Response To Substance [28]
Tissue alpha-L-fucosidase (FUCA1) OTW71IK4 FUCO_HUMAN Increases Response To Substance [28]
GTPase HRas (HRAS) OTWQN0DP RASH_HUMAN Decreases Response To Substance [28]
Epidermal growth factor receptor kinase substrate 8 (EPS8) OTZ6ES6V EPS8_HUMAN Increases Response To Substance [28]
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⏷ Show the Full List of 65 DOT(s)

References

1 ClinicalTrials.gov (NCT00078572) Capecitabine (XELODA) With Or Without Lapatinib (GW572016) For Women With Refractory Advanced or Metastatic Breast Cancer
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: 5692).
3 Lapatinib FDA Label
4 Capecitabine FDA Label
5 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: 6799).
6 UGT-dependent regioselective glucuronidation of ursodeoxycholic acid and obeticholic acid and selective transport of the consequent acyl glucuronides by OATP1B1 and 1B3. Chem Biol Interact. 2019 Sep 1;310:108745. doi: 10.1016/j.cbi.2019.108745. Epub 2019 Jul 9.
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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.
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20 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.
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35 A carboxylesterase 2 gene polymorphism as predictor of capecitabine on response and time to progression. Curr Drug Metab. 2008 May;9(4):336-43. doi: 10.2174/138920008784220646.