Details of the Drug Combination

General Information of Drug Combination (ID: DCUI661)

Drug Combination Name
PD-0325901 Lapatinib
Indication
Disease Entry Status REF
Colon adenocarcinoma Investigative [1]
Component Drugs PD-0325901   DM27D4J Lapatinib   DM3BH1Y
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: LOVO
Zero Interaction Potency (ZIP) Score: 0.33
Bliss Independence Score: 0.26
Loewe Additivity Score: 6.24
LHighest Single Agent (HSA) Score: 12.97

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of PD-0325901
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 2 [2]
PD-0325901 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MAPK/ERK kinase kinase (MAP3K) TTROQ37 NOUNIPROTAC Modulator [6]
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PD-0325901 Interacts with 84 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Increases Expression [7]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Increases Expression [7]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Increases Expression [7]
Nuclear receptor subfamily 0 group B member 2 (NR0B2) OT7UVICX NR0B2_HUMAN Decreases Expression [7]
Toll-like receptor 4 (TLR4) OTP7ML3S TLR4_HUMAN Decreases Expression [5]
Neuropilin-1 (NRP1) OTCGULYV NRP1_HUMAN Decreases Expression [5]
T-box transcription factor TBX3 (TBX3) OTM64N7K TBX3_HUMAN Decreases Expression [5]
Protein sprouty homolog 2 (SPRY2) OTH0CRCZ SPY2_HUMAN Decreases Expression [5]
Leupaxin (LPXN) OTUNV3CK LPXN_HUMAN Decreases Expression [5]
PR domain zinc finger protein 1 (PRDM1) OTQLSVBS PRDM1_HUMAN Decreases Expression [5]
Slit homolog 2 protein (SLIT2) OTLS2RJ4 SLIT2_HUMAN Decreases Expression [5]
Tumor necrosis factor ligand superfamily member 15 (TNFSF15) OTNGA2BW TNF15_HUMAN Decreases Expression [5]
Integrin beta-like protein 1 (ITGBL1) OTJDHE17 ITGBL_HUMAN Decreases Expression [5]
Urokinase-type plasminogen activator (PLAU) OTX0QGKK UROK_HUMAN Decreases Expression [5]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Decreases Expression [5]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Decreases Expression [5]
Glycophorin-C (GYPC) OTOEDR7O GLPC_HUMAN Decreases Expression [5]
Growth-regulated alpha protein (CXCL1) OT3WCTZV GROA_HUMAN Decreases Expression [5]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [5]
Tissue factor pathway inhibitor (TFPI) OTA0FX16 TFPI1_HUMAN Decreases Expression [5]
Mast/stem cell growth factor receptor Kit (KIT) OTHUY3VZ KIT_HUMAN Decreases Expression [5]
Aminopeptidase N (ANPEP) OTP3WYFD AMPN_HUMAN Decreases Expression [5]
Integrin alpha-2 (ITGA2) OTPFL017 ITA2_HUMAN Decreases Expression [5]
Protein-glutamine gamma-glutamyltransferase 2 (TGM2) OT6MFOWF TGM2_HUMAN Decreases Expression [5]
Pentraxin-related protein PTX3 (PTX3) OTPXHRKU PTX3_HUMAN Decreases Expression [5]
5-hydroxytryptamine receptor 7 (HTR7) OT44DEWB 5HT7R_HUMAN Decreases Expression [5]
Glutaredoxin-1 (GLRX) OT0QHTAR GLRX1_HUMAN Decreases Expression [5]
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) OT3K7HY5 DHB2_HUMAN Decreases Expression [5]
ETS translocation variant 5 (ETV5) OTE2OBM4 ETV5_HUMAN Decreases Expression [5]
ETS translocation variant 4 (ETV4) OT8C98UZ ETV4_HUMAN Decreases Expression [5]
Transcription factor SOX-9 (SOX9) OTVDJFGN SOX9_HUMAN Decreases Expression [5]
ETS translocation variant 1 (ETV1) OT6PMJIK ETV1_HUMAN Decreases Expression [5]
Stanniocalcin-1 (STC1) OTGVVXYF STC1_HUMAN Decreases Expression [5]
Paired mesoderm homeobox protein 1 (PRRX1) OTTZK5G8 PRRX1_HUMAN Decreases Expression [5]
Epithelial membrane protein 1 (EMP1) OTSZHUHQ EMP1_HUMAN Decreases Expression [5]
Forkhead box protein G1 (FOXG1) OTAW57J4 FOXG1_HUMAN Decreases Expression [5]
ADP-ribosylation factor-like protein 4C (ARL4C) OTQ3QNNU ARL4C_HUMAN Decreases Expression [5]
Reelin (RELN) OTLKMW1O RELN_HUMAN Decreases Expression [5]
C-C motif chemokine 20 (CCL20) OTUCJY4N CCL20_HUMAN Decreases Expression [5]
A-kinase anchor protein 12 (AKAP12) OTCVRDDX AKA12_HUMAN Decreases Expression [5]
Urokinase plasminogen activator surface receptor (PLAUR) OTIRKKEQ UPAR_HUMAN Decreases Expression [5]
Dual specificity protein phosphatase 4 (DUSP4) OT6WAO12 DUS4_HUMAN Decreases Expression [5]
Semaphorin-3A (SEMA3A) OTQJSV7W SEM3A_HUMAN Decreases Expression [5]
Monocyte to macrophage differentiation factor (MMD) OTB5I4OC PAQRB_HUMAN Decreases Expression [5]
Syntaxin-1A (STX1A) OTSBUZB4 STX1A_HUMAN Decreases Expression [5]
Dual specificity protein phosphatase 6 (DUSP6) OT4H6RKW DUS6_HUMAN Decreases Expression [5]
Kinesin-like protein KIF24 (KIF24) OTJTA5V3 KIF24_HUMAN Decreases Expression [5]
Anoctamin-1 (ANO1) OTSREUNI ANO1_HUMAN Decreases Expression [5]
NADH-cytochrome b5 reductase 2 (CYB5R2) OTTLM7XN NB5R2_HUMAN Decreases Expression [5]
Dynamin-binding protein (DNMBP) OTMHH14H DNMBP_HUMAN Decreases Expression [5]
Sialic acid-binding Ig-like lectin 15 (SIGLEC15) OTON4K9S SIG15_HUMAN Decreases Expression [5]
UPF0606 protein KIAA1549L (KIAA1549L) OT80HUVY K154L_HUMAN Decreases Expression [5]
Neuron navigator 3 (NAV3) OT97M1TR NAV3_HUMAN Decreases Expression [5]
Dedicator of cytokinesis protein 4 (DOCK4) OTH3XY8B DOCK4_HUMAN Decreases Expression [5]
Transmembrane protein 156 (TMEM156) OTH7YJID TM156_HUMAN Decreases Expression [5]
Tribbles homolog 2 (TRIB2) OTHSX3MX TRIB2_HUMAN Decreases Expression [5]
Hyaluronan synthase 2 (HAS2) OTTD3PAL HYAS2_HUMAN Decreases Expression [5]
Neuronal cell adhesion molecule (NRCAM) OT80HHQ2 NRCAM_HUMAN Decreases Expression [5]
Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) OTB71I02 DCBD2_HUMAN Decreases Expression [5]
Formin-like protein 2 (FMNL2) OT9OVWCV FMNL2_HUMAN Decreases Expression [5]
Monoglyceride lipase (MGLL) OT5ES4IE MGLL_HUMAN Decreases Expression [5]
Paternally-expressed gene 3 protein (PEG3) OTHQW98S PEG3_HUMAN Decreases Expression [5]
Disintegrin and metalloproteinase domain-containing protein 19 (ADAM19) OTH88TXU ADA19_HUMAN Decreases Expression [5]
Sodium-dependent neutral amino acid transporter B(0)AT2 (SLC6A15) OTGMPVNR S6A15_HUMAN Decreases Expression [5]
Endothelial cell-specific molecule 1 (ESM1) OT331Y8V ESM1_HUMAN Decreases Expression [5]
Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1) OTW3T4B2 IRPL1_HUMAN Decreases Expression [5]
Neurotrimin (NTM) OTHF0UQU NTRI_HUMAN Decreases Expression [5]
Histone deacetylase 9 (HDAC9) OTO8O0LF HDAC9_HUMAN Decreases Expression [5]
Type 2 lactosamine alpha-2,3-sialyltransferase (ST3GAL6) OTB17Q43 SIA10_HUMAN Decreases Expression [5]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [8]
Forkhead box protein O3 (FOXO3) OTHXQG4P FOXO3_HUMAN Increases Expression [9]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [10]
DNA excision repair protein ERCC-1 (ERCC1) OTNPYQHI ERCC1_HUMAN Decreases Expression [11]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [12]
Fos-related antigen 1 (FOSL1) OT9YTYMB FOSL1_HUMAN Decreases Expression [13]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [14]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [14]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [12]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Decreases Phosphorylation [15]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Decreases Activity [16]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Decreases Expression [8]
Bcl-2 homologous antagonist/killer (BAK1) OTDP6ILW BAK_HUMAN Increases Expression [12]
DNA repair endonuclease XPF (ERCC4) OTFIOPG1 XPF_HUMAN Increases Expression [11]
Ras-related C3 botulinum toxin substrate 1 (RAC1) OTKRO61U RAC1_HUMAN Affects Response To Substance [17]
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⏷ Show the Full List of 84 DOT(s)
Indication(s) of Lapatinib
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [3]
Gastroesophageal junction adenocarcinoma 2B71 Approved [4]
Melanoma 2C30 Approved [4]
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 [19]
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [19]
Eukaryotic elongation factor 2 kinase (eEF-2K) TT1QFLA EF2K_HUMAN Inhibitor [20]
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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 [21]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [22]
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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 [23]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [24]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Metabolism [23]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [24]
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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 [25]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [26]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Increases Expression [27]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [27]
NAD(P)H dehydrogenase 1 (NQO1) OTZGGIVK NQO1_HUMAN Increases Expression [27]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Activity [27]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Decreases Expression [28]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Activity [25]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [29]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [30]
DNA topoisomerase 1 (TOP1) OT51O0CF TOP1_HUMAN Decreases Expression [31]
DNA topoisomerase 2-alpha (TOP2A) OT6LPS08 TOP2A_HUMAN Decreases Expression [31]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Increases Expression [31]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Decreases Expression [29]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [32]
Receptor tyrosine-protein kinase erbB-3 (ERBB3) OTRSST0A ERBB3_HUMAN Decreases Activity [33]
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Increases Secretion [34]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [25]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Activity [29]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Activity [29]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Decreases Activity [25]
DNA replication licensing factor MCM7 (MCM7) OT6FXC6K MCM7_HUMAN Decreases Expression [29]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [31]
Cyclin-dependent kinase inhibitor 1B (CDKN1B) OTNY5LLZ CDN1B_HUMAN Increases Expression [25]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [31]
Caspase-9 (CASP9) OTD4RFFG CASP9_HUMAN Increases Activity [31]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Expression [30]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Decreases Activity [35]
GTPase KRas (KRAS) OT78QCN8 RASK_HUMAN Decreases Response To Substance [36]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1) OTC6GISG DQA1_HUMAN Increases ADR [37]
Zinc finger protein SNAI1 (SNAI1) OTDPYAMC SNAI1_HUMAN Decreases Response To Substance [38]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Increases Metabolism [31]
Cytochrome P450 3A7 (CYP3A7) OTTCDHHM CP3A7_HUMAN Increases Metabolism [31]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Response To Substance [38]
Tenascin-X (TNXB) OTVBWAV5 TENX_HUMAN Increases ADR [37]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1) OTVVI3UI DQB1_HUMAN Increases ADR [37]
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⏷ Show the Full List of 36 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Ewing sarcoma-peripheral primitive neuroectodermal tumour DCERNQ6 ES2 Investigative [39]
Breast carcinoma DCKKNGJ KPL1 Investigative [1]
Breast carcinoma DC2J4BT OCUBM Investigative [1]
Carcinoma DCR6XGK EFM192B Investigative [1]
Carcinoma DC6PCU2 MDAMB436 Investigative [1]
Colon carcinoma DCJRTDJ RKO Investigative [1]
Invasive ductal carcinoma DCCB57U T-47D Investigative [1]
Rectal adenocarcinoma DCUY2HO SW837 Investigative [1]
Adenocarcinoma DCXSDN6 CAOV3 Investigative [40]
Adenocarcinoma DCXJO0W A427 Investigative [40]
Adenocarcinoma DCR78NF NCIH1650 Investigative [40]
Adenocarcinoma DCVT3VI NCIH2122 Investigative [40]
Adenocarcinoma DCOJZFW NCIH23 Investigative [40]
Adenocarcinoma DC0HN10 NCIH520 Investigative [40]
Adenocarcinoma DC94F7Y COLO320DM Investigative [40]
Adenocarcinoma DCQQMQK DLD1 Investigative [40]
Amelanotic melanoma DCLP8DL A2058 Investigative [40]
Germ cell tumour DCMASXK PA1 Investigative [40]
Malignant melanoma DCXY24W HT144 Investigative [40]
Malignant melanoma DCQH2CL RPMI7951 Investigative [40]
Malignant melanoma DC6XLIR SKMEL30 Investigative [40]
Malignant melanoma DCHTPI1 UACC62 Investigative [40]
Mesothelioma DCN7XNQ MSTO Investigative [40]
Non small cell carcinoma DC7BUTH SKMES1 Investigative [40]
Ovarian endometrioid adenocarcinoma DCEJZX3 A2780 Investigative [40]
Ovarian serous cystadenocarcinoma DC1XLUB SK-OV-3 Investigative [40]
Prostate carcinoma DC51RDB VCAP Investigative [40]
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⏷ Show the Full List of 27 DrugCom(s)

References

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37 HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breast cancer. J Clin Oncol. 2011 Feb 20;29(6):667-73. doi: 10.1200/JCO.2010.31.3197. Epub 2011 Jan 18.
38 Niclosamide inhibits epithelial-mesenchymal transition and tumor growth in lapatinib-resistant human epidermal growth factor receptor 2-positive breast cancer. Int J Biochem Cell Biol. 2016 Feb;71:12-23. doi: 10.1016/j.biocel.2015.11.014. Epub 2015 Nov 28.
39 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.
40 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.