General Information of Drug Combination (ID: DCIZKVL)

Drug Combination Name
Estramustine MK-1775
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Estramustine   DMWTAOI MK-1775   DM3WDZ5
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SW-620
Zero Interaction Potency (ZIP) Score: 1.46
Bliss Independence Score: 0.09
Loewe Additivity Score: 0.88
LHighest Single Agent (HSA) Score: 4.76

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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 [5]
------------------------------------------------------------------------------------
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 [6]
------------------------------------------------------------------------------------
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 [7]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Phosphorylation [8]
------------------------------------------------------------------------------------
Indication(s) of MK-1775
Disease Entry ICD 11 Status REF
Ovarian cancer 2C73 Phase 2 [3]
Solid tumour/cancer 2A00-2F9Z Phase 1 [4]
MK-1775 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Wee1-like protein kinase (WEE1) TTJFOAL WEE1_HUMAN Inhibitor [10]
------------------------------------------------------------------------------------
MK-1775 Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cyclin-dependent kinase 1 (CDK1) OTW1SC2N CDK1_HUMAN Decreases Phosphorylation [9]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Increases Response To Substance [9]
------------------------------------------------------------------------------------

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Ewing sarcoma-peripheral primitive neuroectodermal tumour DCXBAE9 ES2 Investigative [11]
Breast and ovarian cancer syndrome DC8RIYX UWB1289 Investigative [12]
Breast carcinoma DC05PAU OCUBM Investigative [12]
Carcinoma DCL04CS EFM192B Investigative [12]
Colon adenocarcinoma DCFP73J LOVO Investigative [12]
Invasive ductal carcinoma DCCGIN3 T-47D Investigative [12]
Adenocarcinoma DC32TT3 CAOV3 Investigative [1]
Adenocarcinoma DCYRSFL A427 Investigative [1]
Adenocarcinoma DCMW6FP NCIH2122 Investigative [1]
Adenocarcinoma DC5Q9HY NCIH520 Investigative [1]
Adenocarcinoma DCSF1LK COLO320DM Investigative [1]
Adenocarcinoma DC61LSG DLD1 Investigative [1]
Adenocarcinoma DCA5QO6 HT29 Investigative [1]
Amelanotic melanoma DCASYQW A2058 Investigative [1]
Germ cell tumour DCS0RVF PA1 Investigative [1]
Malignant melanoma DCLJNJ2 A375 Investigative [1]
Malignant melanoma DCO8IQQ HT144 Investigative [1]
Malignant melanoma DCS0WS5 RPMI7951 Investigative [1]
Malignant melanoma DCE6FX0 SKMEL30 Investigative [1]
Mesothelioma DC9SD03 MSTO Investigative [1]
Non small cell carcinoma DC8484L SKMES1 Investigative [1]
Ovarian endometrioid adenocarcinoma DCJBZYW A2780 Investigative [1]
------------------------------------------------------------------------------------
⏷ Show the Full List of 22 DrugCom(s)

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 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7702).
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Estramustine binding protein in primary tumours and metastases of malignant melanoma. Melanoma Res. 1994 Dec;4(6):401-5.
6 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.
7 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.
8 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.
9 Functional kinomics identifies candidate therapeutic targets in head and neck cancer. Clin Cancer Res. 2014 Aug 15;20(16):4274-88. doi: 10.1158/1078-0432.CCR-13-2858.
10 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.
11 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.
12 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.