Details of the Drug Combination

General Information of Drug Combination (ID: DCGCSIS)

• Drug Combination Name: Trifluridine + Lapatinib
• Indication: Minimally invasive lung adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Trifluridine (DMG2YBD): Small molecular drug
  Lapatinib (DM3BH1Y): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: NCI-H322M
  Zero Interaction Potency (ZIP) Score: 9.74
  Bliss Independence Score: 9.91
  Loewe Additivity Score: 9.63
  LHighest Single Agent (HSA) Score: 10.99

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Trifluridine

Disease Entry	ICD 11	Status	REF
Herpetic keratitis	1F00.10	Approved	[2]
Virus infection	1A24-1D9Z	Approved	[3]
Colon cancer	2B90.Z	Investigative	[2]

Trifluridine 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	[6]

Trifluridine Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[7]
Concentrative nucleoside transporter 1 (SLC28A1)	DT0EQPW	S28A1_HUMAN	Substrate	[8]
Equilibrative nucleoside transporter 1 (SLC29A1)	DTXD1TQ	S29A1_HUMAN	Substrate	[8]
Equilibrative nucleoside transporter 2 (SLC29A2)	DTW78DQ	S29A2_HUMAN	Substrate	[8]

Trifluridine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Thymidine phosphorylase (TYMP)	DE4HCYL	TYPH_HUMAN	Metabolism	[9]

Trifluridine Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[10]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Affects Activity	[11]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Increases Cleavage	[12]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[12]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[12]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Cleavage	[12]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Activity	[13]

Indication(s) of Lapatinib

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[4]
Gastroesophageal junction adenocarcinoma	2B71	Approved	[5]
Melanoma	2C30	Approved	[5]

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	[15]
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[15]
Eukaryotic elongation factor 2 kinase (eEF-2K)	TT1QFLA	EF2K_HUMAN	Inhibitor	[16]

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	[17]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[18]

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	[19]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[20]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[19]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[20]

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	[21]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[22]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[23]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[23]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Expression	[23]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Activity	[23]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[24]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Activity	[21]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[25]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[26]
DNA topoisomerase 1 (TOP1)	OT51O0CF	TOP1_HUMAN	Decreases Expression	[27]
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Decreases Expression	[27]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[27]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[25]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[28]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Decreases Activity	[29]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[30]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[21]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Activity	[25]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Activity	[25]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Activity	[21]
DNA replication licensing factor MCM7 (MCM7)	OT6FXC6K	MCM7_HUMAN	Decreases Expression	[25]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[27]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[21]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[27]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[27]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[26]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[31]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Decreases Response To Substance	[32]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)	OTC6GISG	DQA1_HUMAN	Increases ADR	[33]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Decreases Response To Substance	[34]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Metabolism	[27]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Increases Metabolism	[27]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Response To Substance	[34]
Tenascin-X (TNXB)	OTVBWAV5	TENX_HUMAN	Increases ADR	[33]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Increases ADR	[33]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCEZ8HA	NCIH23	Investigative	[1]
Cutaneous melanoma	DCUD2AQ	SK-MEL-28	Investigative	[1]
Pleural epithelioid mesothelioma	DC88WBS	NCI-H226	Investigative	[1]

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