Details of the Drug Combination

General Information of Drug Combination (ID: DCZVHAE)

• Drug Combination Name: Dacarbazine + Fludarabine
• Indication: Glioma; Status: Investigative [1]
• Component Drugs:
  Dacarbazine (DMNPZL4): Small molecular drug
  Fludarabine (DMVRLT7): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SF-268
  Zero Interaction Potency (ZIP) Score: 0.25
  Bliss Independence Score: 5.62
  Loewe Additivity Score: 5.35
  LHighest Single Agent (HSA) Score: 7.44

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 Fludarabine

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[4]
Cutaneous melanoma	2C30	Approved	[4]
Haematological malignancy	2B33.Y	Approved	[5]
Hematologic disease	3C0Z	Approved	[4]
Hepatosplenic T-cell lymphoma	N.A.	Approved	[4]
Immunodeficiency	4A00-4A85	Approved	[4]
Large granular lymphocytic leukemia	2A90.1	Approved	[4]
Lung cancer	2C25.0	Approved	[4]
MALT lymphoma	N.A.	Approved	[4]
Multiple sclerosis	8A40	Approved	[4]
Myeloproliferative neoplasm	2A20	Approved	[4]
Nodal marginal zone lymphoma	2A85.0	Approved	[4]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified	N.A.	Approved	[4]
Recurrent adult burkitt lymphoma	2A85.6	Approved	[4]
Small intestine lymphoma	N.A.	Approved	[4]
Splenic marginal zone lymphoma	N.A.	Approved	[4]
Systemic lupus erythematosus	4A40.0	Approved	[4]
Systemic sclerosis	4A42	Approved	[4]
Testicular lymphoma	N.A.	Approved	[4]
Classic Hodgkin lymphoma	N.A.	Investigative	[4]
Colon cancer	2B90.Z	Investigative	[4]
Gastric cancer	2B72	Investigative	[4]
Neuroblastoma	2D11.2	Investigative	[4]

Fludarabine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adenosine deaminase (ADA)	TTLP57V	ADA_HUMAN	Inhibitor	[23]

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	[24]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Increases Expression	[25]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[25]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Increases Expression	[26]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Increases Expression	[27]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[20]
Tumor necrosis factor receptor superfamily member 6 (FAS)	OTP9XG86	TNR6_HUMAN	Increases Expression	[28]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Decreases Expression	[29]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Phosphorylation	[21]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Phosphorylation	[21]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Activity	[30]
Dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2)	OTUE7Z91	MP2K2_HUMAN	Increases Activity	[30]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[26]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[28]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN)	OTOWDUNT	PTEN_HUMAN	Increases Expression	[29]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1)	OT4Y9NQI	MP2K1_HUMAN	Increases Activity	[30]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[27]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[27]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[28]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Decreases Expression	[21]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[22]
Growth/differentiation factor 15 (GDF15)	OTWQN50N	GDF15_HUMAN	Increases Expression	[26]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Large cell lung carcinoma	DC8H3RO	NCI-H460	Investigative	[1]
Plasma cell myeloma	DCGD7TN	RPMI-8226	Investigative	[1]

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