Details of the Drug Combination

General Information of Drug Combination (ID: DCRRNX6)

Drug Combination Name
Estramustine Valrubicin
Indication
Disease Entry Status REF
Childhood T acute lymphoblastic leukemia Investigative [1]
Component Drugs Estramustine   DMWTAOI Valrubicin   DMOYJFK
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL is unavailable
High-throughput Screening Result Testing Cell Line: CCRF-CEM
Zero Interaction Potency (ZIP) Score: 9.52
Bliss Independence Score: 11.97
Loewe Additivity Score: 3.73
LHighest Single Agent (HSA) Score: 10.94

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 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]
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Indication(s) of Valrubicin
Disease Entry ICD 11 Status REF
Bladder cancer 2C94 Approved [2]
In situ carcinoma N.A. Approved [3]
Urinary bladder cancer N.A. Approved [3]
Psoriasis vulgaris EA90 Phase 2 [4]
Valrubicin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
DNA topoisomerase II (TOP2) TT0IHXV TOP2A_HUMAN; TOP2B_HUMAN Inhibitor [9]
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Valrubicin Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [10]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adult acute myeloid leukemia DCET2N6 HL-60(TB) Investigative [1]
Adult T acute lymphoblastic leukemia DC7R4IV MOLT-4 Investigative [1]
Anaplastic large cell lymphoma DCWA0K8 SR Investigative [1]
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References

1 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.
2 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3 Valrubicin FDA Label
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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 Metabolic activation of N-acylanthracyclines precedes their interaction with DNA topoisomerase II. NCI Monogr. 1987;(4):111-5.
10 A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.