General Information of Drug Combination (ID: DCLDLW2)

Drug Combination Name
Fosfomycin Hydroxychloroquine
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Fosfomycin   DMVGPMX Hydroxychloroquine   DMSIVND
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: 1.58
Bliss Independence Score: 1.58
Loewe Additivity Score: 15.37
LHighest Single Agent (HSA) Score: 15.37

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Fosfomycin
Disease Entry ICD 11 Status REF
Bacterial infection 1A00-1C4Z Approved [2]
Urinary tract infection GC08 Approved [3]
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 [7]
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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 [8]
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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 [9]
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Indication(s) of Hydroxychloroquine
Disease Entry ICD 11 Status REF
Chronic renal failure GB61.Z Approved [4]
Malaria 1F40-1F45 Approved [5]
Plasmodium falciparum malaria 1F40 Approved [4]
Plasmodium malariae malaria N.A. Approved [4]
Plasmodium ovale malaria N.A. Approved [4]
Systemic lupus erythematosus 4A40.0 Approved [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [6]
Colon cancer 2B90.Z Investigative [4]
Hydroxychloroquine Interacts with 4 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HUMAN pH-dependent viral fusion/replication (pH-DVF/R) TTD16BI N.A. Inhibitor [10]
HUMAN glycosylation of host receptor (GHR) TTZGK1R N.A. Inhibitor [10]
Toll-like receptor 7 (TLR7) TTRJ1K4 TLR7_HUMAN Antagonist [11]
HUMAN toll-like receptor 7/9 signalling pathway (TLR7/9 pathway) TT3A1EZ N.A. Inhibitor [12]
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Hydroxychloroquine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [13]
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Hydroxychloroquine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [14]
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Hydroxychloroquine Interacts with 30 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Decreases Activity [15]
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) OTPGHZB9 IFIT3_HUMAN Increases Expression [16]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Decreases Expression [17]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1) OTY9R6FZ ERN1_HUMAN Increases Expression [16]
Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1) OT4TMERS NFAC1_HUMAN Affects Expression [18]
Claudin-1 (CLDN1) OT27KV99 CLD1_HUMAN Increases Expression [19]
Interferon beta (IFNB1) OTYQGUB5 IFNB_HUMAN Increases Expression [16]
C-X-C motif chemokine 10 (CXCL10) OTTLQ6S0 CXL10_HUMAN Increases Expression [16]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Affects Expression [20]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL) OTG7J4BP PPBT_HUMAN Affects Expression [20]
Transcription factor Jun (JUN) OTCYBO6X JUN_HUMAN Increases Phosphorylation [16]
Cathepsin B (CTSB) OTP9G5QB CATB_HUMAN Affects Localization [21]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Expression [22]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [23]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [23]
NF-kappa-B inhibitor alpha (NFKBIA) OTFT924M IKBA_HUMAN Increases Degradation [16]
CD40 ligand (CD40LG) OT75Z6A6 CD40L_HUMAN Decreases Expression [18]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [17]
Transcription factor p65 (RELA) OTUJP9CN TF65_HUMAN Increases Expression [16]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Increases Activity [21]
TNF receptor-associated factor 3 (TRAF3) OT5TQBGV TRAF3_HUMAN Increases Expression [16]
Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2) OTK5T6HZ NFAC2_HUMAN Affects Localization [18]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Increases Expression [24]
Interferon regulatory factor 3 (IRF3) OT81U8ME IRF3_HUMAN Increases Phosphorylation [16]
Occludin (OCLN) OTSUTVWL OCLN_HUMAN Increases Expression [19]
Mitochondrial antiviral-signaling protein (MAVS) OTTQ0J64 MAVS_HUMAN Increases Expression [16]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2) OTCA9WCM RSAD2_HUMAN Increases Expression [16]
Interferon-induced helicase C domain-containing protein 1 (IFIH1) OTZA2AHA IFIH1_HUMAN Increases Expression [16]
Toll-like receptor 9 (TLR9) OTFZ45HX TLR9_HUMAN Decreases Expression [25]
7-dehydrocholesterol reductase (DHCR7) OTLILBUI DHCR7_HUMAN Affects Expression [20]
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⏷ Show the Full List of 30 DOT(s)

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 Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
3 Fosfomycin FDA Label
4 Hydroxychloroquine FDA Label
5 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: 7198).
6 ClinicalTrials.gov (NCT04341727) Hydroxychloroquine,Hydroxychloroquine,Azithromycin in the Treatment of SARS CoV-2 Infection (WU352). U.S. National Institutes of Health.
7 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.
8 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.
9 [Successful treatment of MRSA-associated glomerulonephritis with antibiotic therapy]. Nihon Jinzo Gakkai Shi. 2003;45(1):37-41.
10 Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271.
11 TLR7/9 antagonists as therapeutics for immune-mediated inflammatory disorders. Inflamm Allergy Drug Targets. 2007 Dec;6(4):223-35.
12 Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020 Mar;16(3):155-166.
13 MDR-ABC transporters: biomarkers in rheumatoid arthritis. Clin Exp Rheumatol. 2013 Sep-Oct;31(5):779-87.
14 Hydroxychloroquine: a physiologically-based pharmacokinetic model in the context of cancer-related autophagy modulation. J Pharmacol Exp Ther. 2018 Jun;365(3):447-459.
15 Somer M, Kallio J, Pesonen U, Pyykko K, Huupponen R, Scheinin M "Influence of hydroxychloroquine on the bioavailability of oral metoprolol." Br J Clin Pharmacol 49 (2000): 549-54. [PMID: 10848718]
16 Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. J Interferon Cytokine Res. 2015 Mar;35(3):143-56. doi: 10.1089/jir.2014.0038. Epub 2014 Oct 16.
17 Hydroxychloroquine potentiates Fas-mediated apoptosis of rheumatoid synoviocytes. Clin Exp Immunol. 2006 Jun;144(3):503-11. doi: 10.1111/j.1365-2249.2006.03070.x.
18 Hydroxychloroquine inhibits CD154 expression in CD4(+) T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017 Aug 9;19(1):183. doi: 10.1186/s13075-017-1393-y.
19 Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability. J Biochem Mol Toxicol. 2015 Jul;29(7):299-304. doi: 10.1002/jbt.21696. Epub 2015 Mar 9.
20 Hydroxychloroquine decreases human MSC-derived osteoblast differentiation and mineralization in vitro. J Cell Mol Med. 2018 Feb;22(2):873-882. doi: 10.1111/jcmm.13373. Epub 2017 Oct 3.
21 Mitochondrial membrane permeabilization is a critical step of lysosome-initiated apoptosis induced by hydroxychloroquine. Oncogene. 2003 Jun 19;22(25):3927-36. doi: 10.1038/sj.onc.1206622.
22 Attenuation of chloroquine and hydroxychloroquine on the invasive potential of bladder cancer through targeting matrix metalloproteinase 2 expression. Environ Toxicol. 2021 Nov;36(11):2138-2145. doi: 10.1002/tox.23328. Epub 2021 Jul 19.
23 Reactive oxygen species mediate chloroquine-induced expression of chemokines by human astroglial cells. Glia. 2004 Jul;47(1):9-20. doi: 10.1002/glia.20017.
24 d-galactose induces premature senescence of lens epithelial cells by disturbing autophagy flux and mitochondrial functions. Toxicol Lett. 2018 Jun 1;289:99-106. doi: 10.1016/j.toxlet.2018.02.001. Epub 2018 Feb 6.
25 Antagonist-mediated down-regulation of Toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus. Arthritis Res Ther. 2012 Apr 18;14(2):R80. doi: 10.1186/ar3803.