Details of the Drug Combination

General Information of Drug Combination (ID: DC5RZNI)

• Drug Combination Name: Fludarabine + Lapatinib
• Indication: Invasive ductal carcinoma; Status: Investigative [1]
• Component Drugs:
  Fludarabine (DMVRLT7): Small molecular drug
  Lapatinib (DM3BH1Y): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: T-47D
  Zero Interaction Potency (ZIP) Score: 2.99
  Bliss Independence Score: 10.16
  Loewe Additivity Score: 1.35
  LHighest Single Agent (HSA) Score: 3.61

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Fludarabine

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[2]
Cutaneous melanoma	2C30	Approved	[2]
Haematological malignancy	2B33.Y	Approved	[3]
Hematologic disease	3C0Z	Approved	[2]
Hepatosplenic T-cell lymphoma	N.A.	Approved	[2]
Immunodeficiency	4A00-4A85	Approved	[2]
Large granular lymphocytic leukemia	2A90.1	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
MALT lymphoma	N.A.	Approved	[2]
Multiple sclerosis	8A40	Approved	[2]
Myeloproliferative neoplasm	2A20	Approved	[2]
Nodal marginal zone lymphoma	2A85.0	Approved	[2]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[2]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[2]
Small intestine lymphoma	N.A.	Approved	[2]
Splenic marginal zone lymphoma	N.A.	Approved	[2]
Systemic lupus erythematosus	4A40.0	Approved	[2]
Systemic sclerosis	4A42	Approved	[2]
Testicular lymphoma	N.A.	Approved	[2]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]
Colon cancer	2B90.Z	Investigative	[2]
Gastric cancer	2B72	Investigative	[2]
Neuroblastoma	2D11.2	Investigative	[2]

Fludarabine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adenosine deaminase (ADA)	TTLP57V	ADA_HUMAN	Inhibitor	[9]

Fludarabine Interacts with 22 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A)	OTBPCU2O	TR10A_HUMAN	Affects Expression	[10]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[11]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[11]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Increases Expression	[12]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Increases Expression	[13]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[6]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[14]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Decreases Expression	[15]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[7]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[7]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Activity	[16]
Dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2)	OTUE7Z91	MP2K2_HUMAN	Increases Activity	[16]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[12]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[14]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)	OTOWDUNT	PTEN_HUMAN	Increases Expression	[15]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1)	OT4Y9NQI	MP2K1_HUMAN	Increases Activity	[16]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[13]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[13]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[14]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Decreases Expression	[7]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[8]
Growth/differentiation factor 15 (GDF15)	OTWQN50N	GDF15_HUMAN	Increases Expression	[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	[18]
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[18]
Eukaryotic elongation factor 2 kinase (eEF-2K)	TT1QFLA	EF2K_HUMAN	Inhibitor	[19]

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	[20]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[21]

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	[22]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[23]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[22]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[23]

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	[24]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[25]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[26]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[26]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Expression	[26]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Activity	[26]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[27]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Activity	[24]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[28]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[29]
DNA topoisomerase 1 (TOP1)	OT51O0CF	TOP1_HUMAN	Decreases Expression	[30]
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Decreases Expression	[30]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[30]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[28]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[31]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Decreases Activity	[32]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[33]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[24]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Activity	[28]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Activity	[28]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Activity	[24]
DNA replication licensing factor MCM7 (MCM7)	OT6FXC6K	MCM7_HUMAN	Decreases Expression	[28]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[30]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[24]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[30]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[30]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[29]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[34]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Decreases Response To Substance	[35]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)	OTC6GISG	DQA1_HUMAN	Increases ADR	[36]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Decreases Response To Substance	[37]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Metabolism	[30]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Increases Metabolism	[30]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Response To Substance	[37]
Tenascin-X (TNXB)	OTVBWAV5	TENX_HUMAN	Increases ADR	[36]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Increases ADR	[36]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DC44OE7	HCT-15	Investigative	[38]

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