Details of the Drug Combination

General Information of Drug Combination (ID: DCAXEWF)

• Drug Combination Name: Vincristine + Lapatinib
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Vincristine (DMINOX3): Small molecular drug
  Lapatinib (DM3BH1Y): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HCT116
  Zero Interaction Potency (ZIP) Score: 17.79
  Bliss Independence Score: 20.35
  Loewe Additivity Score: 13.23
  LHighest Single Agent (HSA) Score: 12.77

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vincristine

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[2]
Adult kidney Wilms tumor	N.A.	Approved	[3]
Beckwith-Wiedemann syndrome	N.A.	Approved	[3]
Burkitt lymphoma	N.A.	Approved	[3]
Central nervous system neoplasm	N.A.	Approved	[3]
Childhood acute lymphoblastic leukemia	N.A.	Approved	[3]
Childhood kidney Wilms tumor	N.A.	Approved	[3]
Hamartoma	N.A.	Approved	[3]
Kidney neoplasm	N.A.	Approved	[3]
Leukemia	N.A.	Approved	[3]
MALT lymphoma	N.A.	Approved	[3]
Nodal marginal zone lymphoma	2A85.0	Approved	[3]
Plasma cell myeloma	2A83.1	Approved	[3]
Primitive neuroectodermal tumor	N.A.	Approved	[3]
Splenic marginal zone lymphoma	N.A.	Approved	[3]
Testicular lymphoma	N.A.	Approved	[3]
Wilms tumor	N.A.	Approved	[3]
Classic Hodgkin lymphoma	N.A.	Investigative	[3]
Follicular lymphoma	2A80	Investigative	[3]
Neuroblastoma	2D11.2	Investigative	[3]

Vincristine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Modulator	[6]

Vincristine Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[7]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[8]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[10]

Vincristine Interacts with 3 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	[11]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[12]

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	[14]
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[14]
Eukaryotic elongation factor 2 kinase (eEF-2K)	TT1QFLA	EF2K_HUMAN	Inhibitor	[15]

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	[16]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[17]

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	[18]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[19]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[18]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[19]

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	[20]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[21]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[22]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[22]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Expression	[22]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Activity	[22]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[23]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Activity	[20]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[24]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[25]
DNA topoisomerase 1 (TOP1)	OT51O0CF	TOP1_HUMAN	Decreases Expression	[26]
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Decreases Expression	[26]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[26]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[24]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[27]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Decreases Activity	[28]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[29]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[20]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Activity	[24]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Activity	[24]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Activity	[20]
DNA replication licensing factor MCM7 (MCM7)	OT6FXC6K	MCM7_HUMAN	Decreases Expression	[24]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[26]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[20]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[26]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[26]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[25]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[30]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Decreases Response To Substance	[31]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)	OTC6GISG	DQA1_HUMAN	Increases ADR	[32]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Decreases Response To Substance	[33]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Metabolism	[26]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Increases Metabolism	[26]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Response To Substance	[33]
Tenascin-X (TNXB)	OTVBWAV5	TENX_HUMAN	Increases ADR	[32]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Increases ADR	[32]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DC3CSL3	DU-145	Investigative	[1]
Adenocarcinoma	DCS6AOK	OVCAR3	Investigative	[1]
Adenocarcinoma	DC2CW35	A549	Investigative	[1]
Adenocarcinoma	DC7F25A	HT29	Investigative	[1]
Adenocarcinoma	DC9E34Q	HCT-15	Investigative	[1]
Clear cell renal cell carcinoma	DC7SW5S	A498	Investigative	[1]
Clear cell renal cell carcinoma	DCFX50Q	786-0	Investigative	[1]
Clear cell renal cell carcinoma	DCV4YT8	CAKI-1	Investigative	[1]
Cutaneous melanoma	DCFVIES	SK-MEL-28	Investigative	[1]
Glioma	DCWICSW	SF-268	Investigative	[1]
Glioma	DC0FN9T	SF-295	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCYF3AJ	OVCAR-4	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC63BGT	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCLQ3GA	NCI\\/ADR-RES	Investigative	[1]
Lung adenocarcinoma	DC1YV4Y	HOP-62	Investigative	[1]
Lung adenocarcinoma	DCMWEFA	EKVX	Investigative	[1]
Melanoma	DC7EVSN	UACC-257	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCD56FH	NCI-H322M	Investigative	[1]
Non-small cell lung carcinoma	DCKPCHI	HOP-92	Investigative	[1]
Prostate carcinoma	DCO5VI5	PC-3	Investigative	[1]
Renal cell carcinoma	DCRQUU8	SN12C	Investigative	[1]
Breast adenocarcinoma	DCSJ0U9	MDA-MB-468	Investigative	[34]
Invasive ductal carcinoma	DC7AJIN	HS 578T	Investigative	[34]
Invasive ductal carcinoma	DC2OUYJ	T-47D	Investigative	[34]

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