Details of the Drug Combination

General Information of Drug Combination (ID: DCHUIOX)

• Drug Combination Name: Lapatinib + Pemetrexed
• Indication: Lung Cancer, Non-Small Cell; Status: Phase 1 [1]
• Component Drugs:
  Lapatinib (DM3BH1Y): Small molecular drug
  Pemetrexed (DMMX2E6): Small molecular drug

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	[7]
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[7]
Eukaryotic elongation factor 2 kinase (eEF-2K)	TT1QFLA	EF2K_HUMAN	Inhibitor	[8]

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]

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]

Lapatinib Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[13]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[14]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[15]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[16]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[17]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[18]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Decreases Activity	[19]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Activity	[16]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Activity	[16]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[20]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)	OTC6GISG	DQA1_HUMAN	Increases ADR	[21]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Decreases Response To Substance	[22]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Response To Substance	[22]
Tenascin-X (TNXB)	OTVBWAV5	TENX_HUMAN	Increases ADR	[21]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Increases ADR	[21]

Indication(s) of Pemetrexed

Disease Entry	ICD 11	Status	REF
Central nervous system lymphoma	2B33.5	Approved	[4]
Epithelioid mesothelioma	2F10	Approved	[4]
Lung cancer	2C25.0	Approved	[4]
Malignant pleural mesothelioma	2C26.0	Approved	[5]
Non-small-cell lung cancer	2C25.Y	Approved	[4]
Sarcomatoid mesothelioma	N.A.	Approved	[4]
Small-cell lung cancer	2C25.Y	Approved	[4]
Lung neoplasm	N.A.	Investigative	[4]

Pemetrexed 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	[25]

Pemetrexed Interacts with 6 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[26]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[27]
Multidrug resistance-associated protein 5 (ABCC5)	DTYVM24	MRP5_HUMAN	Substrate	[28]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[29]
Folate transporter 1 (SLC19A1)	DTOSN46	S19A1_HUMAN	Substrate	[30]
Proton-coupled folate transporter (SLC46A1)	DTDJEMI	PCFT_HUMAN	Substrate	[31]

Pemetrexed Interacts with 11 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Reduced folate transporter (SLC19A1)	OTWB0BTO	S19A1_HUMAN	Increases Response To Substance	[32]
ATP-binding cassette sub-family C member 5 (ABCC5)	OT34G4US	MRP5_HUMAN	Decreases Response To Substance	[33]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[34]
DNA excision repair protein ERCC-1 (ERCC1)	OTNPYQHI	ERCC1_HUMAN	Decreases Expression	[35]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[36]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[37]
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (MTHFD2)	OT1LQSGX	MTDC_HUMAN	Increases Response To Substance	[38]
Splicing factor 45 (RBM17)	OT9ROJCL	SPF45_HUMAN	Decreases Response To Substance	[39]
ATP-binding cassette sub-family C member 11 (ABCC11)	OTVHL7OR	MRP8_HUMAN	Decreases Response To Substance	[40]
Folylpolyglutamate synthase, mitochondrial (FPGS)	OTW3F1ZE	FOLC_HUMAN	Increases Response To Substance	[24]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Response To Substance	[34]

References

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