Details of the Drug Combination

General Information of Drug Combination (ID: DCO4MNH)

• Drug Combination Name: Lapatinib + PD-0325901
• Indication: Ewing sarcoma-peripheral primitive neuroectodermal tumour; Status: Investigative [1]
• Component Drugs:
  Lapatinib (DM3BH1Y): Small molecular drug
  PD-0325901 (DM27D4J): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: ES2
  Zero Interaction Potency (ZIP) Score: 1.93
  Bliss Independence Score: 5.18
  Loewe Additivity Score: 4.95
  LHighest Single Agent (HSA) Score: 6.87

Molecular Interaction Atlas of This Drug Combination

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]

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]

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]

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]

Indication(s) of PD-0325901

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Phase 2	[4]

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	[27]

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	[28]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Expression	[28]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Increases Expression	[28]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Decreases Expression	[28]
Toll-like receptor 4 (TLR4)	OTP7ML3S	TLR4_HUMAN	Decreases Expression	[26]
Neuropilin-1 (NRP1)	OTCGULYV	NRP1_HUMAN	Decreases Expression	[26]
T-box transcription factor TBX3 (TBX3)	OTM64N7K	TBX3_HUMAN	Decreases Expression	[26]
Protein sprouty homolog 2 (SPRY2)	OTH0CRCZ	SPY2_HUMAN	Decreases Expression	[26]
Leupaxin (LPXN)	OTUNV3CK	LPXN_HUMAN	Decreases Expression	[26]
PR domain zinc finger protein 1 (PRDM1)	OTQLSVBS	PRDM1_HUMAN	Decreases Expression	[26]
Slit homolog 2 protein (SLIT2)	OTLS2RJ4	SLIT2_HUMAN	Decreases Expression	[26]
Tumor necrosis factor ligand superfamily member 15 (TNFSF15)	OTNGA2BW	TNF15_HUMAN	Decreases Expression	[26]
Integrin beta-like protein 1 (ITGBL1)	OTJDHE17	ITGBL_HUMAN	Decreases Expression	[26]
Urokinase-type plasminogen activator (PLAU)	OTX0QGKK	UROK_HUMAN	Decreases Expression	[26]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[26]
Interstitial collagenase (MMP1)	OTI4I2V1	MMP1_HUMAN	Decreases Expression	[26]
Glycophorin-C (GYPC)	OTOEDR7O	GLPC_HUMAN	Decreases Expression	[26]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Decreases Expression	[26]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[26]
Tissue factor pathway inhibitor (TFPI)	OTA0FX16	TFPI1_HUMAN	Decreases Expression	[26]
Mast/stem cell growth factor receptor Kit (KIT)	OTHUY3VZ	KIT_HUMAN	Decreases Expression	[26]
Aminopeptidase N (ANPEP)	OTP3WYFD	AMPN_HUMAN	Decreases Expression	[26]
Integrin alpha-2 (ITGA2)	OTPFL017	ITA2_HUMAN	Decreases Expression	[26]
Protein-glutamine gamma-glutamyltransferase 2 (TGM2)	OT6MFOWF	TGM2_HUMAN	Decreases Expression	[26]
Pentraxin-related protein PTX3 (PTX3)	OTPXHRKU	PTX3_HUMAN	Decreases Expression	[26]
5-hydroxytryptamine receptor 7 (HTR7)	OT44DEWB	5HT7R_HUMAN	Decreases Expression	[26]
Glutaredoxin-1 (GLRX)	OT0QHTAR	GLRX1_HUMAN	Decreases Expression	[26]
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)	OT3K7HY5	DHB2_HUMAN	Decreases Expression	[26]
ETS translocation variant 5 (ETV5)	OTE2OBM4	ETV5_HUMAN	Decreases Expression	[26]
ETS translocation variant 4 (ETV4)	OT8C98UZ	ETV4_HUMAN	Decreases Expression	[26]
Transcription factor SOX-9 (SOX9)	OTVDJFGN	SOX9_HUMAN	Decreases Expression	[26]
ETS translocation variant 1 (ETV1)	OT6PMJIK	ETV1_HUMAN	Decreases Expression	[26]
Stanniocalcin-1 (STC1)	OTGVVXYF	STC1_HUMAN	Decreases Expression	[26]
Paired mesoderm homeobox protein 1 (PRRX1)	OTTZK5G8	PRRX1_HUMAN	Decreases Expression	[26]
Epithelial membrane protein 1 (EMP1)	OTSZHUHQ	EMP1_HUMAN	Decreases Expression	[26]
Forkhead box protein G1 (FOXG1)	OTAW57J4	FOXG1_HUMAN	Decreases Expression	[26]
ADP-ribosylation factor-like protein 4C (ARL4C)	OTQ3QNNU	ARL4C_HUMAN	Decreases Expression	[26]
Reelin (RELN)	OTLKMW1O	RELN_HUMAN	Decreases Expression	[26]
C-C motif chemokine 20 (CCL20)	OTUCJY4N	CCL20_HUMAN	Decreases Expression	[26]
A-kinase anchor protein 12 (AKAP12)	OTCVRDDX	AKA12_HUMAN	Decreases Expression	[26]
Urokinase plasminogen activator surface receptor (PLAUR)	OTIRKKEQ	UPAR_HUMAN	Decreases Expression	[26]
Dual specificity protein phosphatase 4 (DUSP4)	OT6WAO12	DUS4_HUMAN	Decreases Expression	[26]
Semaphorin-3A (SEMA3A)	OTQJSV7W	SEM3A_HUMAN	Decreases Expression	[26]
Monocyte to macrophage differentiation factor (MMD)	OTB5I4OC	PAQRB_HUMAN	Decreases Expression	[26]
Syntaxin-1A (STX1A)	OTSBUZB4	STX1A_HUMAN	Decreases Expression	[26]
Dual specificity protein phosphatase 6 (DUSP6)	OT4H6RKW	DUS6_HUMAN	Decreases Expression	[26]
Kinesin-like protein KIF24 (KIF24)	OTJTA5V3	KIF24_HUMAN	Decreases Expression	[26]
Anoctamin-1 (ANO1)	OTSREUNI	ANO1_HUMAN	Decreases Expression	[26]
NADH-cytochrome b5 reductase 2 (CYB5R2)	OTTLM7XN	NB5R2_HUMAN	Decreases Expression	[26]
Dynamin-binding protein (DNMBP)	OTMHH14H	DNMBP_HUMAN	Decreases Expression	[26]
Sialic acid-binding Ig-like lectin 15 (SIGLEC15)	OTON4K9S	SIG15_HUMAN	Decreases Expression	[26]
UPF0606 protein KIAA1549L (KIAA1549L)	OT80HUVY	K154L_HUMAN	Decreases Expression	[26]
Neuron navigator 3 (NAV3)	OT97M1TR	NAV3_HUMAN	Decreases Expression	[26]
Dedicator of cytokinesis protein 4 (DOCK4)	OTH3XY8B	DOCK4_HUMAN	Decreases Expression	[26]
Transmembrane protein 156 (TMEM156)	OTH7YJID	TM156_HUMAN	Decreases Expression	[26]
Tribbles homolog 2 (TRIB2)	OTHSX3MX	TRIB2_HUMAN	Decreases Expression	[26]
Hyaluronan synthase 2 (HAS2)	OTTD3PAL	HYAS2_HUMAN	Decreases Expression	[26]
Neuronal cell adhesion molecule (NRCAM)	OT80HHQ2	NRCAM_HUMAN	Decreases Expression	[26]
Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2)	OTB71I02	DCBD2_HUMAN	Decreases Expression	[26]
Formin-like protein 2 (FMNL2)	OT9OVWCV	FMNL2_HUMAN	Decreases Expression	[26]
Monoglyceride lipase (MGLL)	OT5ES4IE	MGLL_HUMAN	Decreases Expression	[26]
Paternally-expressed gene 3 protein (PEG3)	OTHQW98S	PEG3_HUMAN	Decreases Expression	[26]
Disintegrin and metalloproteinase domain-containing protein 19 (ADAM19)	OTH88TXU	ADA19_HUMAN	Decreases Expression	[26]
Sodium-dependent neutral amino acid transporter B(0)AT2 (SLC6A15)	OTGMPVNR	S6A15_HUMAN	Decreases Expression	[26]
Endothelial cell-specific molecule 1 (ESM1)	OT331Y8V	ESM1_HUMAN	Decreases Expression	[26]
Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1)	OTW3T4B2	IRPL1_HUMAN	Decreases Expression	[26]
Neurotrimin (NTM)	OTHF0UQU	NTRI_HUMAN	Decreases Expression	[26]
Histone deacetylase 9 (HDAC9)	OTO8O0LF	HDAC9_HUMAN	Decreases Expression	[26]
Type 2 lactosamine alpha-2,3-sialyltransferase (ST3GAL6)	OTB17Q43	SIA10_HUMAN	Decreases Expression	[26]
Bcl-2-like protein 11 (BCL2L11)	OTNQQWFJ	B2L11_HUMAN	Increases Expression	[29]
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Increases Expression	[30]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[31]
DNA excision repair protein ERCC-1 (ERCC1)	OTNPYQHI	ERCC1_HUMAN	Decreases Expression	[32]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[33]
Fos-related antigen 1 (FOSL1)	OT9YTYMB	FOSL1_HUMAN	Decreases Expression	[34]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[35]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[35]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[33]
Small ribosomal subunit protein eS6 (RPS6)	OTT4D1LN	RS6_HUMAN	Decreases Phosphorylation	[36]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Decreases Activity	[37]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[29]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[33]
DNA repair endonuclease XPF (ERCC4)	OTFIOPG1	XPF_HUMAN	Increases Expression	[32]
Ras-related C3 botulinum toxin substrate 1 (RAC1)	OTKRO61U	RAC1_HUMAN	Affects Response To Substance	[38]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast and ovarian cancer syndrome	DCN0E7E	UWB1289	Investigative	[39]
Breast and ovarian cancer syndrome	DCL98IZ	UWB1289+BRCA1	Investigative	[39]
Breast carcinoma	DCZY7TD	ZR751	Investigative	[39]
Breast carcinoma	DC909I2	KPL1	Investigative	[39]
Breast carcinoma	DCBGYAK	OCUBM	Investigative	[39]
Carcinoma	DCGP215	OV90	Investigative	[39]
Carcinoma	DCK8EQV	EFM192B	Investigative	[39]
Carcinoma	DCMEXFB	MDAMB436	Investigative	[39]
Colon adenocarcinoma	DCJSORG	LOVO	Investigative	[39]
Colon carcinoma	DCJ5A6D	RKO	Investigative	[39]
Invasive ductal carcinoma	DCJ3U73	T-47D	Investigative	[39]
Rectal adenocarcinoma	DCUCGP5	SW837	Investigative	[39]
Adenocarcinoma	DCJLIXT	CAOV3	Investigative	[1]
Adenocarcinoma	DCQDUXE	OVCAR3	Investigative	[1]
Adenocarcinoma	DCI4N4J	A427	Investigative	[1]
Adenocarcinoma	DCN9156	NCIH1650	Investigative	[1]
Adenocarcinoma	DC7Q9B6	NCIH2122	Investigative	[1]
Adenocarcinoma	DCWPX30	NCIH23	Investigative	[1]
Adenocarcinoma	DC078BX	NCIH520	Investigative	[1]
Adenocarcinoma	DCQMU7N	COLO320DM	Investigative	[1]
Adenocarcinoma	DCWGBCD	DLD1	Investigative	[1]
Adenocarcinoma	DCHBSZJ	HT29	Investigative	[1]
Amelanotic melanoma	DC5OTT4	A2058	Investigative	[1]
Germ cell tumour	DCZ9V28	PA1	Investigative	[1]
Large cell lung carcinoma	DCGNIMN	NCI-H460	Investigative	[1]
Malignant melanoma	DCGTD23	HT144	Investigative	[1]
Malignant melanoma	DCS4RNP	RPMI7951	Investigative	[1]
Malignant melanoma	DCFVMNF	UACC62	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DCSAETK	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DC0YFC7	SK-OV-3	Investigative	[1]
Prostate carcinoma	DCAII4H	LNCAP	Investigative	[1]
Prostate carcinoma	DCMOFZ7	VCAP	Investigative	[1]

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