General Information of Drug Combination (ID: DC3D80F)

Drug Combination Name
Zileuton Fosfomycin
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Zileuton   DMVRIC2 Fosfomycin   DMVGPMX
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 14.27
Bliss Independence Score: 14.27
Loewe Additivity Score: 30.36
LHighest Single Agent (HSA) Score: 30.36

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Zileuton
Disease Entry ICD 11 Status REF
Allergic asthma CA23.0 Approved [2]
Asthma CA23 Approved [3]
Intrinsic asthma N.A. Approved [2]
Zileuton Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Arachidonate 5-lipoxygenase (5-LOX) TT2J34L LOX5_HUMAN Inhibitor [6]
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Zileuton Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [8]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [9]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [7]
Prostaglandin G/H synthase 1 (COX-1) DE073H6 PGH1_HUMAN Metabolism [7]
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Zileuton Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Activity [10]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Decreases Activity [11]
Polyunsaturated fatty acid 5-lipoxygenase (ALOX5) OT7FOIK2 LOX5_HUMAN Decreases Activity [12]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2) OTHF4H9U DHI2_HUMAN Increases Activity [12]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [13]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [14]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [14]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Affects Response To Substance [15]
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⏷ Show the Full List of 8 DOT(s)
Indication(s) of Fosfomycin
Disease Entry ICD 11 Status REF
Bacterial infection 1A00-1C4Z Approved [4]
Urinary tract infection GC08 Approved [5]
Fosfomycin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bacterial UDP-N-acetylglucosamine carboxyvinyltransferase (Bact murA) TTICX3S MURA_ECOLI Inhibitor [16]
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Fosfomycin Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Glutathione S-transferase alpha-1 (GSTA1) DE4ZHS1 GSTA1_HUMAN Metabolism [17]
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Fosfomycin Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
C-reactive protein (CRP) OT0RFT8F CRP_HUMAN Decreases Expression [18]
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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 Zileuton FDA Label
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: 5297).
4 Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
5 Fosfomycin FDA Label
6 5-lipoxygenase inhibitor zileuton attenuates ischemic brain damage: involvement of matrix metalloproteinase 9. Neurol Res. 2009 Oct;31(8):848-52.
7 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
8 Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218.
9 Identification of the human liver cytochrome P450 enzymes involved in the metabolism of zileuton (ABT-077) and its N-dehydroxylated metabolite, Abbott-66193. Drug Metab Dispos. 1995 Oct;23(10):1163-74.
10 Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.
11 Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. Drug Metab Dispos. 2003 Nov;31(11):1352-60.
12 Prostaglandins and leukotriene B4 are potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 2 activity in human choriocarcinoma JEG-3 cells. Biol Reprod. 1999 Jul;61(1):40-5.
13 Zileuton, a new efficient and safe systemic anti-acne drug. Dermatoendocrinol. 2009 May;1(3):188-92. doi: 10.4161/derm.1.3.8368.
14 Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease. Toxicol Sci. 2012 Oct;129(2):346-62. doi: 10.1093/toxsci/kfs208. Epub 2012 Jun 14.
15 5-lipoxygenase pharmacogenetics in asthma: overlap with Cys-leukotriene receptor antagonist loci. Pharmacogenet Genomics. 2009 Mar;19(3):244-7. doi: 10.1097/FPC.0b013e328326e0b1.
16 Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release. J Biol Chem. 2005 Feb 4;280(5):3757-63.
17 Formation of an adduct between fosfomycin and glutathione: a new mechanism of antibiotic resistance in bacteria. Antimicrob Agents Chemother. 1988 Oct;32(10):1552-6.
18 [Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy]. Nihon Jinzo Gakkai Shi. 2003;45(1):37-41.