Details
Stereochemistry | ACHIRAL |
Molecular Formula | C4H10NO5P |
Molecular Weight | 183.0997 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
ON(CCCP(O)(O)=O)C=O
InChI
InChIKey=GJXWDTUCERCKIX-UHFFFAOYSA-N
InChI=1S/C4H10NO5P/c6-4-5(7)2-1-3-11(8,9)10/h4,7H,1-3H2,(H2,8,9,10)
Molecular Formula | C4H10NO5P |
Molecular Weight | 183.0997 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/12937969Curator's Comment: The description was created based on several sources, including
https://www.drugbank.ca/drugs/DB02948 | https://clinicaltrials.gov/ct2/show/NCT00214643 | https://clinicaltrials.gov/ct2/show/NCT00217451 | https://www.ncbi.nlm.nih.gov/pubmed/21866890
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12937969
Curator's Comment: The description was created based on several sources, including
https://www.drugbank.ca/drugs/DB02948 | https://clinicaltrials.gov/ct2/show/NCT00214643 | https://clinicaltrials.gov/ct2/show/NCT00217451 | https://www.ncbi.nlm.nih.gov/pubmed/21866890
Fosmidomycin (3-(formylhydroxyamino)-propylphosphonic acid mono-sodium salt, 3-(N-formyl-N-hydroxyamino)-propylphosphonic acid mono-sodium salt, FR-31564) is a potent inhibitor of P. falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (PfDXR), developed by Albert Schweitzer Hospital for P. falciparum malaria treatment. Fosmidomycin was originally isolated as natural antibiotic from Streptomyces lavendulae. Fosmidomycin is active against a broad range of enterobacteria, but not against Gram-positive organisms or anaerobes. Fosmidomycin was developed as far as an early phase II study for the treatment of urinary tract infections by Fujisawa Pharmaceutical Company (Osaka, Japan) in the early eighties, but these trials have been discontinued. In recent clinical studies, it was shown that fosmidomycin is effective in curing uncomplicated Plasmodium falciparum malaria in humans. The treatment was well tolerated and resulted in a fast parasite and fever clearance. However, the high rate of recrudescence precludes the use of fosmidomycin as a monotherapy. In drug combination studies, the synergy of fosmidomycin with clindamycin was observed. Clinical studies with a fosmidomycin-clindamycin combination are currently ongoing.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: O96693 Gene ID: NA Gene Symbol: DXR Target Organism: Plasmodium falciparum (isolate HB3) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12937969 |
28.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4.58 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17531088 |
1200 mg 3 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
FOSMIDOMYCIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2.33 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7073262 |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
FOSMIDOMYCIN serum | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
11.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7073262 |
7.5 mg/kg single, intramuscular dose: 7.5 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered: |
FOSMIDOMYCIN serum | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
27.67 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17531088 |
1200 mg 3 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
FOSMIDOMYCIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
210 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7073262 |
30 mg/kg single, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
FOSMIDOMYCIN serum | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
14 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7073262 |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
FOSMIDOMYCIN serum | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
42.2 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7073262 |
7.5 mg/kg single, intramuscular dose: 7.5 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered: |
FOSMIDOMYCIN serum | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17531088 |
1200 mg 3 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
FOSMIDOMYCIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1.65 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7073262 |
30 mg/kg single, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
FOSMIDOMYCIN serum | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
1.87 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7073262 |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
FOSMIDOMYCIN serum | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
1.58 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7073262 |
7.5 mg/kg single, intramuscular dose: 7.5 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered: |
FOSMIDOMYCIN serum | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
99% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17531088 |
1200 mg 3 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
FOSMIDOMYCIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
PubMed
Title | Date | PubMed |
---|---|---|
The methylerythritol phosphate pathway and its significance as a novel drug target. | 2003 Aug |
|
Methyl palmitate: a novel product of the Medfly (Ceratitis capitata) corpus allatum. | 2003 Dec |
|
Genomics research and malaria control: great expectations. | 2003 Nov |
|
New antimalarial drugs. | 2003 Nov 10 |
|
Fosmidomycin resistance in adenylate cyclase deficient (cya) mutants of Escherichia coli. | 2003 Sep |
|
The heat shock protein 90 of Plasmodium falciparum and antimalarial activity of its inhibitor, geldanamycin. | 2003 Sep 15 |
|
Alternative pathways of carotenoid biosynthesis in prokaryotes and eukaryotes. | 2003 Sep-Oct |
|
The MEP pathway: a new target for the development of herbicides, antibiotics and antimalarial drugs. | 2004 |
|
Impact of ozone on monoterpene emissions and evidence for an isoprene-like antioxidant action of monoterpenes emitted by Quercus ilex leaves. | 2004 Apr |
|
13C labeling reveals chloroplastic and extrachloroplastic pools of dimethylallyl pyrophosphate and their contribution to isoprene formation. | 2004 Aug |
|
Synthesis and biological evaluation with plant cells of new fosmidomycin analogues containing a benzoxazolone or oxazolopyridinone ring. | 2004 Dec |
|
1-Deoxy-D-xylulose 5-phosphate reductoisomerase: an overview. | 2004 Dec |
|
The methylerythritol phosphate pathway is functionally active in all intraerythrocytic stages of Plasmodium falciparum. | 2004 Dec 10 |
|
Distinct light-mediated pathways regulate the biosynthesis and exchange of isoprenoid precursors during Arabidopsis seedling development. | 2004 Jan |
|
Biosynthesis of camptothecin. In silico and in vivo tracer study from [1-13C]glucose. | 2004 Jan |
|
Determination of fosmidomycin in human serum and urine by capillary electrophoresis. | 2004 Jul 5 |
|
Fosmidomycin-clindamycin for Plasmodium falciparum Infections in African children. | 2004 Mar 1 |
|
Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria. | 2004 Nov 1 |
|
Substrate analogs for the investigation of deoxyxylulose 5-phosphate reductoisomerase inhibition: synthesis and evaluation. | 2004 Nov 1 |
|
Molecular cloning and functional expression of geranylgeranyl pyrophosphate synthase from Coleus forskohlii Briq. | 2004 Nov 18 |
|
Crystallographic structures of two bisphosphonate:1-deoxyxylulose-5-phosphate reductoisomerase complexes. | 2004 Sep 8 |
|
The plastid of Plasmodium spp.: a target for inhibitors. | 2005 |
|
Induction of de novo volatile terpene biosynthesis via cytosolic and plastidial pathways by methyl jasmonate in foliage of Vitis vinifera L. | 2005 Apr 6 |
|
Bacterial genome adaptation to niches: divergence of the potential virulence genes in three Burkholderia species of different survival strategies. | 2005 Dec 7 |
|
Characterization of the Arabidopsis clb6 mutant illustrates the importance of posttranscriptional regulation of the methyl-D-erythritol 4-phosphate pathway. | 2005 Feb |
|
Isoprenoid biosynthesis as a target for antibacterial and antiparasitic drugs: phosphonohydroxamic acids as inhibitors of deoxyxylulose phosphate reducto-isomerase. | 2005 Feb 15 |
|
The crystal structure of E.coli 1-deoxy-D-xylulose-5-phosphate reductoisomerase in a ternary complex with the antimalarial compound fosmidomycin and NADPH reveals a tight-binding closed enzyme conformation. | 2005 Jan 7 |
|
[Prevalence of nonmevalonate and mevalonate pathways for isoprenoid biosynthesis among bacteria of different systematic groups]. | 2005 Mar-Apr |
|
The Arabidopsis csb3 mutant reveals a regulatory link between salicylic acid-mediated disease resistance and the methyl-erythritol 4-phosphate pathway. | 2005 Oct |
|
The capacity for thermal protection of photosynthetic electron transport varies for different monoterpenes in Quercus ilex. | 2005 Sep |
|
Evaluation of fosmidomycin analogs as inhibitors of the Synechocystis sp. PCC6803 1-deoxy-D-xylulose 5-phosphate reductoisomerase. | 2006 Apr 1 |
|
Kinetic characterization of Synechocystis sp. PCC6803 1-deoxy-D-xylulose 5-phosphate reductoisomerase mutants. | 2006 Feb |
|
Involvement of 2-C-methyl-D-erythritol-4-phosphate pathway in biosynthesis of aphidicolin-like tetracyclic diterpene of Scoparia dulcis. | 2006 May |
|
Enhanced flux through the methylerythritol 4-phosphate pathway in Arabidopsis plants overexpressing deoxyxylulose 5-phosphate reductoisomerase. | 2006 Nov |
|
Targeting the methyl erythritol phosphate (MEP) pathway for novel antimalarial, antibacterial and herbicidal drug discovery: inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) enzyme. | 2007 |
|
The methylerythritol phosphate pathway for isoprenoid biosynthesis in coccidia: presence and sensitivity to fosmidomycin. | 2007 Aug |
|
gamma-Substituted bis(pivaloyloxymethyl)ester analogues of fosmidomycin and FR900098. | 2007 Dec |
|
Isoprenoid biosynthesis of the apicoplast as drug target. | 2007 Jan |
|
Conformationally restrained aromatic analogues of fosmidomycin and FR900098. | 2007 Jul |
|
Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum. | 2007 Jun |
|
Structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in a quaternary complex with a magnesium ion, NADPH and the antimalarial drug fosmidomycin. | 2007 Jun 1 |
|
Divergent strategy for the synthesis of alpha-aryl-substituted fosmidomycin analogues. | 2007 May 11 |
|
Pharmacokinetics and pharmacodynamics of fosmidomycin monotherapy and combination therapy with clindamycin in the treatment of multidrug resistant falciparum malaria. | 2007 May 25 |
|
Assessment of in vitro antimalarial interactions between dihydroartemisinin and fosmidomycin. | 2007 Sep |
|
Novel deoxyxylulosephosphate-reductoisomerase inhibitors: fosmidomycin derivatives with spacious acyl residues. | 2007 Sep |
|
Elicitor induced activation of the methylerythritol phosphate pathway toward phytoalexins biosynthesis in rice. | 2007 Sep |
|
Synthesis and evaluation of alpha,beta-unsaturated alpha-aryl-substituted fosmidomycin analogues as DXR inhibitors. | 2007 Sep 1 |
|
Towards new antimalarial drugs: synthesis of non-hydrolyzable phosphate mimics as feed for a predictive QSAR study on 1-deoxy-D-xylulose-5-phosphate reductoisomerase inhibitors. | 2008 Apr |
|
Significance of terpenoids in induced indirect plant defence against herbivorous arthropods. | 2008 Apr |
|
Synthesis of beta- and gamma-oxa isosteres of fosmidomycin and FR900098 as antimalarial candidates. | 2008 Mar 15 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00214643
Fosmidomycin-clindamycin (30 mg/kg and 10 mg/kg) given twice daily for three days
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20718073
Assay mixtures (total volume: 200 mL) contained 100 mm Tris hydrochloride (pH 7.6), 4 mm MnCl2, 0.5 mm dithiothreitol (DTT), 0.5 mm NADPH, 10–30 nm of recombinant IspC protein (P. falciparum) or 100 mm Tris hydrochloride (pH 8.0), 10 mm MgCl2, 1mm NADPH, 27 nm of recombinant IspC protein (E. coli). Dilution series (1:2) of inhibitor 1 (Fosmidomycin) covered the concentration range of 200 mm to 1 nm. The reaction was started by addition of 1-deoxyxylulose 5-phosphate to a final concentration of 1 mm. The reaction was monitored photometrically (room temperature for P. falciparum or 37C for E. coli) at 340 nm in a microplate reader
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:46:57 GMT 2023
by
admin
on
Fri Dec 15 15:46:57 GMT 2023
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Record UNII |
5829E3D9I9
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Record Status |
Validated (UNII)
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Record Version |
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-
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NCI_THESAURUS |
C258
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66508-53-0
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CHEMBL203125
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FOSMIDOMYCIN
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DTXSID70216712
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443725
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C65764
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SUB07802MIG
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5104
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m5554
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C024640
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DB02948
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100000080441
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