Details of the Drug Combination

General Information of Drug Combination (ID: DCOHM0D)

• Drug Combination Name: Dacarbazine + Lapatinib
• Indication: Childhood T acute lymphoblastic leukemia; Status: Investigative [1]
• Component Drugs:
  Dacarbazine (DMNPZL4): Small molecular drug
  Lapatinib (DM3BH1Y): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: CCRF-CEM
  Zero Interaction Potency (ZIP) Score: 6.61
  Bliss Independence Score: 6.55
  Loewe Additivity Score: 3.33
  LHighest Single Agent (HSA) Score: 4

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Dacarbazine

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[2]
Astrocytoma	2A00.0Y	Approved	[2]
Brain disease	8C70-8E61	Approved	[2]
Central nervous system disease	8A04-8D87	Approved	[2]
Glioblastoma	2A00	Approved	[2]
Gliosarcoma	N.A.	Approved	[2]
Melanoma	2C30	Approved	[3]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]
Neuroblastoma	2D11.2	Investigative	[2]

Dacarbazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[7]

Dacarbazine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[8]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[9]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[10]

Dacarbazine Interacts with 12 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Increases Expression	[11]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[6]
Interferon regulatory factor 1 (IRF1)	OT43DI6J	IRF1_HUMAN	Increases Expression	[12]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Decreases Activity	[13]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Response To Substance	[14]
DNA repair nuclease/redox regulator APEX1 (APEX1)	OT53OI14	APEX1_HUMAN	Increases Response To Substance	[15]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Response To Substance	[16]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Response To Substance	[17]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Response To Substance	[17]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Affects Response To Substance	[18]
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1)	OTS3FVTY	M3K1_HUMAN	Decreases Response To Substance	[17]
Erythropoietin (EPO)	OTZ90CN4	EPO_HUMAN	Decreases Response To Substance	[19]

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	[21]
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[21]
Eukaryotic elongation factor 2 kinase (eEF-2K)	TT1QFLA	EF2K_HUMAN	Inhibitor	[22]

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	[23]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[24]

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	[25]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[26]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[25]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[26]

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	[27]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[28]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Increases Expression	[29]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[29]
NAD(P)H dehydrogenase 1 (NQO1)	OTZGGIVK	NQO1_HUMAN	Increases Expression	[29]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Activity	[29]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[30]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Activity	[27]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[31]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[32]
DNA topoisomerase 1 (TOP1)	OT51O0CF	TOP1_HUMAN	Decreases Expression	[33]
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Decreases Expression	[33]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[33]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[31]
Phosphatidylcholine translocator ABCB4 (ABCB4)	OTE6PY83	MDR3_HUMAN	Decreases Activity	[34]
Receptor tyrosine-protein kinase erbB-3 (ERBB3)	OTRSST0A	ERBB3_HUMAN	Decreases Activity	[35]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[36]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[27]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Activity	[31]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Activity	[31]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Activity	[27]
DNA replication licensing factor MCM7 (MCM7)	OT6FXC6K	MCM7_HUMAN	Decreases Expression	[31]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[33]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[27]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[33]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[33]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[32]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[37]
GTPase KRas (KRAS)	OT78QCN8	RASK_HUMAN	Decreases Response To Substance	[38]
HLA class II histocompatibility antigen, DQ alpha 1 chain (HLA-DQA1)	OTC6GISG	DQA1_HUMAN	Increases ADR	[39]
Zinc finger protein SNAI1 (SNAI1)	OTDPYAMC	SNAI1_HUMAN	Decreases Response To Substance	[40]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Increases Metabolism	[33]
Cytochrome P450 3A7 (CYP3A7)	OTTCDHHM	CP3A7_HUMAN	Increases Metabolism	[33]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Decreases Response To Substance	[40]
Tenascin-X (TNXB)	OTVBWAV5	TENX_HUMAN	Increases ADR	[39]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Increases ADR	[39]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCONUCV	NCIH23	Investigative	[1]
Adenocarcinoma	DCBPCIF	SW-620	Investigative	[1]
Adenocarcinoma	DC5MQGC	HCT-15	Investigative	[1]
Adenocarcinoma	DCHOMR9	HCT116	Investigative	[1]
Adult acute myeloid leukemia	DCVTWBH	HL-60(TB)	Investigative	[1]
Amelanotic melanoma	DCV47KL	MDA-MB-435	Investigative	[1]
Amelanotic melanoma	DC7GYHU	M14	Investigative	[1]
Anaplastic large cell lymphoma	DC5ZLYQ	SR	Investigative	[1]
Astrocytoma	DCBZ75X	SNB-19	Investigative	[1]
Cutaneous melanoma	DCPYPW4	SK-MEL-5	Investigative	[1]
Glioma	DCBFCH4	SF-295	Investigative	[1]
Glioma	DCVBYCQ	SF-268	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCQKYJG	OVCAR-8	Investigative	[1]
Lung adenocarcinoma	DCYBKQM	HOP-62	Investigative	[1]
Malignant melanoma	DCHD6O8	LOX IMVI	Investigative	[1]
Pleural epithelioid mesothelioma	DCVAKD7	NCI-H226	Investigative	[1]

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