Details of the Drug Combination

General Information of Drug Combination (ID: DCZTFSZ)

• Drug Combination Name: Estramustine + MK-5108
• Indication: Germ cell tumour; Status: Investigative [1]
• Component Drugs:
  Estramustine (DMWTAOI): Small molecular drug
  MK-5108 (DMFGYKS): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: PA1
  Zero Interaction Potency (ZIP) Score: 1.55
  Bliss Independence Score: 1.91
  Loewe Additivity Score: 1.33
  LHighest Single Agent (HSA) Score: 5.96

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 2 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]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Phosphorylation	[7]

Indication(s) of MK-5108

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

MK-5108 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aurora kinase B (AURKB)	TT5LS6T	AURKB_HUMAN	Inhibitor	[8]
Aurora kinase A (AURKA)	TTPS3C0	AURKA_HUMAN	Inhibitor	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Ewing sarcoma-peripheral primitive neuroectodermal tumour	DCTUOIW	ES2	Investigative	[9]
Breast carcinoma	DCK59SF	OCUBM	Investigative	[10]
Carcinoma	DC94B58	EFM192B	Investigative	[10]
Colon carcinoma	DC77C9F	RKO	Investigative	[10]
Adenocarcinoma	DCROSU1	CAOV3	Investigative	[1]
Adenocarcinoma	DCFLH11	NCIH23	Investigative	[1]
Adenocarcinoma	DCR2FV7	COLO320DM	Investigative	[1]
Adenocarcinoma	DC1VTGF	DLD1	Investigative	[1]
Adenocarcinoma	DC2NERJ	HT29	Investigative	[1]
Amelanotic melanoma	DCJ70UI	A2058	Investigative	[1]
Malignant melanoma	DCGMPWJ	A375	Investigative	[1]
Malignant melanoma	DCD30UN	RPMI7951	Investigative	[1]
Malignant melanoma	DCRJN2P	SKMEL30	Investigative	[1]
Malignant melanoma	DC6RPZ8	UACC62	Investigative	[1]
Mesothelioma	DCZU85E	MSTO	Investigative	[1]
Ovarian endometrioid adenocarcinoma	DCYIFMU	A2780	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCBIT89	SK-OV-3	Investigative	[1]

References

• [1] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] ClinicalTrials.gov (NCT00543387) Treatment of Participants With Advanced and/or Refractory Solid Tumors (MK-5108-001 AM4). U.S. National Institutes of Health.
• [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] Induction of apoptosis by estramustine phosphate mediated by phosphorylation of bcl-2. J Neurooncol. 2001 Aug;54(1):23-9. doi: 10.1023/a:1012566601485.
• [8] A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
• [9] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [10] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.