Details of the Drug Combination

General Information of Drug Combination (ID: DCJG6SL)

Drug Combination Name
Uracil mustard Ixabepilone
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs Uracil mustard   DMHL7OB Ixabepilone   DM2OZ3G
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: NCIH23
Zero Interaction Potency (ZIP) Score: 0.68
Bliss Independence Score: 1.54
Loewe Additivity Score: 0.74
LHighest Single Agent (HSA) Score: 0.94

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 [6]
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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 [7]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Increases ADR [7]
Granulocyte-macrophage colony-stimulating factor (CSF2) OT1M7D28 CSF2_HUMAN Increases ADR [7]
Poly polymerase 1 (PARP1) OTIESHK4 PARP1_ARATH Increases ADR [7]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Increases ADR [7]
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Indication(s) of Ixabepilone
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [4]
Breast carcinoma N.A. Approved [5]
Ixabepilone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Tubulin (TUB) TTML2WA NOUNIPROTAC Stablizer [8]
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Ixabepilone Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
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Ixabepilone Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [10]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Anaplastic large cell lymphoma DCE8RHF SR Investigative [11]
Childhood T acute lymphoblastic leukemia DCMCOYR CCRF-CEM Investigative [11]
Papillary renal cell carcinoma DC8KJHD ACHN Investigative [11]
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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 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 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: 6824).
5 Ixabepilone FDA Label
6 Excision of DNA adducts of nitrogen mustards by bacterial and mammalian 3-methyladenine-DNA glycosylases. Carcinogenesis. 1996 Apr;17(4):643-8.
7 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.
8 Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
9 Ixabepilone, a novel microtubule-targeting agent for breast cancer, is a substrate for P-glycoprotein (P-gp/MDR1/ABCB1) but not breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther. 2011 May;337(2):423-32.
10 The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of ixabepilone: a first in class epothilone B analogue in late-phase clinical development. Clin Cancer Res. 2008 May 1;14(9):2701-9.
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.