Details of the Drug Combination

General Information of Drug Combination (ID: DCTSBC5)

• Drug Combination Name: Estramustine + Bendamustine hydrochloride
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Estramustine (DMWTAOI): Small molecular drug
  Bendamustine hydrochloride (DMFH15Z): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HCT116
  Zero Interaction Potency (ZIP) Score: 1.39
  Bliss Independence Score: 1.47
  Loewe Additivity Score: 2.32
  LHighest Single Agent (HSA) Score: 3.58

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Estramustine

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[2]

Estramustine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estramustine binding protein (EMBP)	TTSBFYK	NOUNIPROTAC	Binder	[4]

Estramustine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]

Estramustine Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Keratin, type I cytoskeletal 18 (KRT18)	OTVLQFIP	K1C18_HUMAN	Increases Expression	[6]

Indication(s) of Bendamustine hydrochloride

Disease Entry	ICD 11	Status	REF
leukaemia	2A60-2B33	Approved	[3]

Bendamustine hydrochloride Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[3]

Bendamustine hydrochloride Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[8]

Bendamustine hydrochloride Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[7]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Decreases Expression	[7]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Expression	[9]
PRKC apoptosis WT1 regulator protein (PAWR)	OTKY7W52	PAWR_HUMAN	Decreases Expression	[7]
Diablo IAP-binding mitochondrial protein (DIABLO)	OTHJ9MCZ	DBLOH_HUMAN	Increases Localization	[7]
Death domain-associated protein 6 (DAXX)	OTX6O7PL	DAXX_HUMAN	Decreases Expression	[7]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Malignant melanoma	DCU55XM	LOX IMVI	Investigative	[1]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [4] Estramustine binding protein in primary tumours and metastases of malignant melanoma. Melanoma Res. 1994 Dec;4(6):401-5.
• [5] Activity of docetaxel with or without estramustine phosphate versus mitoxantrone in androgen dependent and independent human prostate cancer xenografts. J Urol. 2003 May;169(5):1729-34.
• [6] Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles. Br J Cancer. 2006 Jun 5;94(11):1592-8. doi: 10.1038/sj.bjc.6603129.
• [7] Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with down-regulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation. Biochem Pharmacol. 2003 Sep 1;66(5):711-24. doi: 10.1016/s0006-2952(03)00410-6.
• [8] Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites. Cancer Chemother Pharmacol. 2015 Jun;75(6):1143-54.
• [9] Upon drug-induced apoptosis in lymphoma cells X-linked inhibitor of apoptosis (XIAP) translocates from the cytosol to the nucleus. Leuk Lymphoma. 2004 Jul;45(7):1429-36. doi: 10.1080/1042819042000198858.