Natural Product (NP) Details

General Information of the NP (ID: NP4593)
Name
Fosfomycin
Synonyms
FOSFOMYCIN; phosphomycin; Phosphonomycin; 23155-02-4; Fosfonomycin; Fosfocina; Monurol; Veramina; Fosfomicina; Fosfomycine; Fosfomycinum; Antibiotic 833A; [(2R,3S)-3-methyloxiran-2-yl]phosphonic acid; Phosphonic acid, (3-methyloxiranyl)-, (2R-cis)-; UNII-2N81MY12TE; (2R-cis)-(3-Methyloxiranyl)phosphonic acid; (1R,2S)-epoxypropylphosphonic acid; Phosphonemycin; L-cis-1,2-epoxypropylphosphonic acid; (-)-(1R,2S)-(1,2-Epoxypropyl)phosphonic acid; CHEMBL1757; Fosfomycin disodium salt; 2N81MY12TE; CHEBI:28915; FCM; Phosphonic acid, (1,2-epoxypropyl)-, (1R,2S)-(-)-; cis-(1R,2S)-epoxypropylphosphonic acid; 1R-cis-(1,2-epoxypropyl)phosphonic acid; ((2R,3S)-3-methyloxiran-2-yl)phosphonic acid; Fosfomicin; Infectophos; 1,2-EPOXYPROPYLPHOSPHONIC ACID; Levo-phosphonomycin; Fosfomycin (USAN/INN); Fosfomycine [INN-French]; Fosfomycinum [INN-Latin]; Fosfomicina [INN-Spanish]; Fosfomycin [USAN:INN:BAN]; J01XX01; EINECS 245-463-1; MK-955; BRN 1680831; 883A; Fosfomycin (compound 1); Fosfomycinfor culture media; SCHEMBL50951; BIDD:GT0448; BRN 1680831, Fosfocina; ZTI-01; DTXSID4048480; GTPL10813; BCP24891; ZINC1530427; BDBM50024894; cis-(2-Methyloxiranyl)-phosphonic acid; DB00828; (2R,3S)-3-methyloxiran-2-ylphosphonate; 25030-76-6; (1R, 2S)-1,2-epoxypropyl-phosphonic acid; FT-0774116; (2R,3S)-3-methyloxiran-2-ylphosphonic acid; (3-Methyl-oxiranyl)-phosphonic acid(Na salt); C06454; D04253; Q183554; W-107422; BRD-K81101512-234-01-9; Phosphonic acid, P-[(2R,3S)-3-methyl-2-oxiranyl]-; 6F066DFF-696A-4A94-AF78-A28430EBE5BA
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Species Origin Streptomyces fradiae ...     Click to Show/Hide
Streptomyces fradiae
SuperKingdom: Bacteria
Phylum: Actinobacteria
Class: Actinomycetia
Order: Streptomycetales
Family: Streptomycetaceae
Genus: Streptomyces
Species: Streptomyces fradiae
Disease Bacterial infection [ICD-11: 1A00-1C4Z] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.629
 
MDCK Permeability
 -5.03
 
PAMPA
 +
 
HIA
 - - -
 
Distribution
VDss
 -0.496
 
PPB
 6.5%
 
BBB
 ++
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 ++
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 - - -
CYP2B6 inhibitor
 - - -
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 - - -
HLM Stability
 - - -
 
Excretion
CLplasma
 2.475
 
T1/2
 1.942
Toxicity
DILI
 -
 
Rat Oral Acute Toxicity
 - - -
 
FDAMDD
 -
 
Respiratory
 ++
 
Human Hepatotoxicity
 ++
 
Ototoxicity
 ++
 
Drug-induced Nephrotoxicity
 +++
 
Drug-induced Neurotoxicity
 - - -
 
Hematotoxicity
 +
 
Genotoxicity
 +
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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Formula
C3H7O4P
PubChem CID
446987
Canonical SMILES
CC1C(O1)P(=O)(O)O
InChI
1S/C3H7O4P/c1-2-3(7-2)8(4,5)6/h2-3H,1H3,(H2,4,5,6)/t2-,3+/m0/s1
InChIKey
YMDXZJFXQJVXBF-STHAYSLISA-N
CAS Number
CAS 23155-02-4
ChEBI ID
CHEBI:28915
TTD Drug ID
D01GYT
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Ciprofloxacin      Bacterial infection     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Shigella flexneri isolates Microorganism model Shigella flexneri
                    Experimental
                    Result(s)		 Against CIPR S. flexneri isolates, the CIP/FOS combination induced synergy, and increased bacterial killing in vitro and in a simple invertebrate model of infection.
          Linezolid      Bacterial infection     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Staphylococcus aureus strains Microorganism model Staphylococcus aureus
                    Experimental
                    Result(s)		 Linezolid combined with fosfomycin at 4x MIC showed the best synergistic antibacterial effect, and this effect was retained after 24 hours.
          Meropenem      Bacterial infection     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Pseudomonas aeruginosa PAO1 Microorganism model Pseudomonas aeruginosa
                    Experimental
                    Result(s)		 The combination of fosfomycin plus meropenem is synergistic for pseudomonas aeruginosa PAO1 in a hollow-fiber infection model.
          Rifampicin      HIV-infected patients with tuberculosis     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Clinical trial
                    Experimental
                    Result(s)		 In patients with implanted foreign devices, combination therapy was associated with a better long-term outcome.
          N-acetylcysteine      Liver disease     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Escherichia coli strains Microorganism model Escherichia coli
                    Experimental
                    Result(s)		 Fosfomycin and NAC at concentrations achievable in urine displayed a synergistic effect promoting both the formation of biofilms and reduction of sessile cell viability.
          Ceftazidime + Avibactam     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Klebsiella pneumoniae clinical strains Microorganism model Klebseilla pneumoniae
                    Experimental
                    Result(s)		 The combinations of ceftazidime-avibactam with ertapenem, and ceftazidime-avibactam with tigecycline were able to reduce the MIC to less than the susceptibility breakpoint in all KPC- and OXA-48-producing K. pneumoniae.
Target and Pathway
Target(s) Bacterial Enoylpyruvate transferas (Bact murA)  Molecule Info  [8]
References
Reference 1 Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
Reference 2 In vitro and in vivo activity of ciprofloxacin/fosfomycin combination therapy against ciprofloxacin-resistant Shigella flexneri isolates. Infect Drug Resist. 2019 Jun 11;12:1619-1628.
Reference 3 In vitro activity and post-antibiotic effects of linezolid in combination with fosfomycin against clinical isolates of Staphylococcus aureus. Infect Drug Resist. 2018 Nov 1;11:2107-2115.
Reference 4 The Combination of Fosfomycin plus Meropenem Is Synergistic for Pseudomonas aeruginosa PAO1 in a Hollow-Fiber Infection Model. Antimicrob Agents Chemother. 2018 Nov 26;62(12):e01682-18.
Reference 5 Combination therapy with rifampicin or fosfomycin in patients with Staphylococcus aureus bloodstream infection at high risk for complications or relapse: results of a large prospective observational cohort. J Antimicrob Chemother. 2020 Aug 1;75(8):2282-2290.
Reference 6 Effect of fosfomycin alone and in combination with N-acetylcysteine on E. coli biofilms. Int J Antimicrob Agents. 2003 Oct;22 Suppl 2:95-100.
Reference 7 Activity of Ceftazidime-Avibactam Alone and in Combination with Ertapenem, Fosfomycin, and Tigecycline Against Carbapenemase-Producing Klebsiella pneumoniae. Microb Drug Resist. 2019 Nov;25(9):1357-1364.
Reference 8 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.
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