Details of the Drug Combination

General Information of Drug Combination (ID: DCHCIFA)

• Drug Combination Name: Uracil mustard + Dacarbazine
• Indication: Anaplastic large cell lymphoma; Status: Investigative [1]
• Component Drugs:
  Uracil mustard (DMHL7OB): Small molecular drug
  Dacarbazine (DMNPZL4): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SR
  Zero Interaction Potency (ZIP) Score: 6.18
  Bliss Independence Score: 6.26
  Loewe Additivity Score: 6.54
  LHighest Single Agent (HSA) Score: 9.27

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Uracil mustard

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Approved	[2]
Chronic myelogenous leukaemia	2A20.0	Approved	[3]
Polycythemia vera	2A20.4	Approved	[3]
Small lymphocytic lymphoma	2A82.0	Approved	[3]

Uracil mustard Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[6]

Uracil mustard Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
GPI-linked NAD(P)(+)--arginine ADP-ribosyltransferase 1 (ART1)	OT7FBG5W	NAR1_HUMAN	Increases ADR	[7]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases ADR	[7]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Increases ADR	[7]
Poly polymerase 1 (PARP1)	OTIESHK4	PARP1_ARATH	Increases ADR	[7]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases ADR	[7]

Indication(s) of Dacarbazine

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[4]
Astrocytoma	2A00.0Y	Approved	[4]
Brain disease	8C70-8E61	Approved	[4]
Central nervous system disease	8A04-8D87	Approved	[4]
Glioblastoma	2A00	Approved	[4]
Gliosarcoma	N.A.	Approved	[4]
Melanoma	2C30	Approved	[5]
Classic Hodgkin lymphoma	N.A.	Investigative	[4]
Neuroblastoma	2D11.2	Investigative	[4]

Dacarbazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[9]

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	[10]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[11]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[12]

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	[13]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[8]
Interferon regulatory factor 1 (IRF1)	OT43DI6J	IRF1_HUMAN	Increases Expression	[14]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Decreases Activity	[15]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Response To Substance	[16]
DNA repair nuclease/redox regulator APEX1 (APEX1)	OT53OI14	APEX1_HUMAN	Increases Response To Substance	[17]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Response To Substance	[18]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Response To Substance	[19]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Response To Substance	[19]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Affects Response To Substance	[20]
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1)	OTS3FVTY	M3K1_HUMAN	Decreases Response To Substance	[19]
Erythropoietin (EPO)	OTZ90CN4	EPO_HUMAN	Decreases Response To Substance	[21]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Astrocytoma	DCFQZ6O	SNB-19	Investigative	[1]
Glioma	DCM75OP	SF-268	Investigative	[1]
Glioma	DCMHXKW	SF-295	Investigative	[1]
Papillary renal cell carcinoma	DCIYXU0	ACHN	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCOG94U	OVCAR-4	Investigative	[22]
Lung adenocarcinoma	DC2MUIH	EKVX	Investigative	[22]
Melanoma	DCQYK7O	SK-MEL-2	Investigative	[22]
Non-small cell lung carcinoma	DCB9CYN	HOP-92	Investigative	[22]

References

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• [3] Uracil mustard FDA Label
• [4] Dacarbazine FDA Label
• [5] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 075259.
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• [19] Exposure of melanoma cells to dacarbazine results in enhanced tumor growth and metastasis in vivo. J Clin Oncol. 2004 Jun 1;22(11):2092-100. doi: 10.1200/JCO.2004.11.070. Epub 2004 May 3.
• [20] Clusterin regulates drug-resistance in melanoma cells. J Invest Dermatol. 2005 Jun;124(6):1300-7. doi: 10.1111/j.0022-202X.2005.23720.x.
• [21] Functional erythropoietin autocrine loop in melanoma. Am J Pathol. 2005 Mar;166(3):823-30. doi: 10.1016/S0002-9440(10)62303-6.
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