Details of the Drug Combination

General Information of Drug Combination (ID: DCHIETW)

Drug Combination Name
Estramustine Pralatrexate
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Estramustine   DMWTAOI Pralatrexate   DMAO80I
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: HCT116
Zero Interaction Potency (ZIP) Score: 4.1
Bliss Independence Score: 0.94
Loewe Additivity Score: 1.19
LHighest Single Agent (HSA) Score: 1.19

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]
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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]
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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 [7]
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Indication(s) of Pralatrexate
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [3]
Peripheral T-cell lymphoma 2A90.C Approved [3]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [4]
Pralatrexate Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Polypeptide deformylase (PDF) TT9SL3Q DEFM_HUMAN Inhibitor [8]
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Pralatrexate Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Folate transporter 1 (SLC19A1) DTOSN46 S19A1_HUMAN Substrate [9]
Proton-coupled folate transporter (SLC46A1) DTDJEMI PCFT_HUMAN Substrate [9]
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Pralatrexate Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Folylpolyglutamate synthase (FPGS) DECWT2V FOLC_HUMAN Metabolism [10]
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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 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: 6840).
4 Pralatrexate FDA Label
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 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
9 Antifolates in cancer therapy: structure, activity and mechanisms of drug resistance. Drug Resist Updat. 2012 Aug;15(4):183-210.
10 Pralatrexate : evaluation of clinical efficacy and toxicity in T-cell lymphoma. Expert Opin Pharmacother. 2013 Mar;14(4):515-23.