Details of the Drug Combination

General Information of Drug Combination (ID: DCXUD63)

• Drug Combination Name: Dacarbazine + ER819762
• Indication: High grade ovarian serous adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Dacarbazine (DMNPZL4): Small molecular drug
  ER819762 (DMSG91J): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: OVCAR-4
  Zero Interaction Potency (ZIP) Score: 0.07
  Bliss Independence Score: 2.83
  Loewe Additivity Score: 1.72
  LHighest Single Agent (HSA) Score: 1.79

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	[6]

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	[7]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[8]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[9]

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	[10]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[5]
Interferon regulatory factor 1 (IRF1)	OT43DI6J	IRF1_HUMAN	Increases Expression	[11]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Decreases Activity	[12]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Response To Substance	[13]
DNA repair nuclease/redox regulator APEX1 (APEX1)	OT53OI14	APEX1_HUMAN	Increases Response To Substance	[14]
Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)	OTA675TJ	GTR1_HUMAN	Decreases Response To Substance	[15]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Decreases Response To Substance	[16]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Decreases Response To Substance	[16]
Clusterin (CLU)	OTQGG0JM	CLUS_HUMAN	Affects Response To Substance	[17]
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1)	OTS3FVTY	M3K1_HUMAN	Decreases Response To Substance	[16]
Erythropoietin (EPO)	OTZ90CN4	EPO_HUMAN	Decreases Response To Substance	[18]

Indication(s) of ER819762

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[4]

ER819762 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin E2 receptor EP4 (PTGER4)	TT79WV3	PE2R4_HUMAN	Antagonist	[19]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DC55JWU	OVCAR3	Investigative	[1]
Adenocarcinoma	DC0TU4K	HCT116	Investigative	[1]
Adenocarcinoma	DC13SG2	HCC-2998	Investigative	[1]
Adult acute myeloid leukemia	DC511QI	HL-60(TB)	Investigative	[1]
Amelanotic melanoma	DCSJBGF	MDA-MB-435	Investigative	[1]
Anaplastic large cell lymphoma	DCDBIR7	SR	Investigative	[1]
Astrocytoma	DCWXD2Z	SNB-19	Investigative	[1]
Childhood T acute lymphoblastic leukemia	DCNIGPI	CCRF-CEM	Investigative	[1]
Glioma	DCUQIOF	SF-295	Investigative	[1]
Glioma	DCHOFNA	SF-268	Investigative	[1]
Lung adenocarcinoma	DC76J9W	HOP-62	Investigative	[1]
Melanoma	DCU8NGR	UACC-257	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCBFT7X	NCI-H322M	Investigative	[1]
Plasma cell myeloma	DCR5DCZ	RPMI-8226	Investigative	[1]
Colon carcinoma	DCDNXHJ	KM12	Investigative	[20]

References

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• [3] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 075259.
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• [16] 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.
• [17] 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.
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