Details of the Drug Combination

General Information of Drug Combination (ID: DCKNE5Q)

Drug Combination Name
Uracil mustard Estramustine
Indication
Disease Entry Status REF
Adult T acute lymphoblastic leukemia Investigative [1]
Component Drugs Uracil mustard   DMHL7OB Estramustine   DMWTAOI
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: MOLT-4
Zero Interaction Potency (ZIP) Score: 0.06
Bliss Independence Score: 0.69
Loewe Additivity Score: 1.07
LHighest Single Agent (HSA) Score: 4.33

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Uracil mustard
Disease Entry ICD 11 Status REF
Acute myeloid leukaemia 2A60 Approved [2]
Chronic myelogenous leukaemia 2A20.0 Approved [3]
Polycythemia vera 2A20.4 Approved [3]
Small lymphocytic lymphoma 2A82.0 Approved [3]
Uracil mustard Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Modulator [5]
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Uracil mustard Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
GPI-linked NAD(P)(+)--arginine ADP-ribosyltransferase 1 (ART1) OT7FBG5W NAR1_HUMAN Increases ADR [6]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases ADR [6]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Increases ADR [6]
Poly polymerase 1 (PARP1) OTIESHK4 PARP1_ARATH Increases ADR [6]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases ADR [6]
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Indication(s) of Estramustine
Disease Entry ICD 11 Status REF
Prostate cancer 2C82.0 Approved [4]
Estramustine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Estramustine binding protein (EMBP) TTSBFYK NOUNIPROTAC Binder [7]
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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 [8]
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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 [9]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Increases Phosphorylation [10]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Adenocarcinoma DCPVMEB NCIH23 Investigative [11]
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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 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: 7621).
3 Uracil mustard FDA Label
4 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
5 Excision of DNA adducts of nitrogen mustards by bacterial and mammalian 3-methyladenine-DNA glycosylases. Carcinogenesis. 1996 Apr;17(4):643-8.
6 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
7 Estramustine binding protein in primary tumours and metastases of malignant melanoma. Melanoma Res. 1994 Dec;4(6):401-5.
8 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.
9 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.
10 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.
11 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.