Details
Stereochemistry | ACHIRAL |
Molecular Formula | C4H9NO5P.Na |
Molecular Weight | 205.0815 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].ON(CCCP(O)([O-])=O)C=O
InChI
InChIKey=ZZPUYRHMTGOTEU-UHFFFAOYSA-M
InChI=1S/C4H10NO5P.Na/c6-4-5(7)2-1-3-11(8,9)10;/h4,7H,1-3H2,(H2,8,9,10);/q;+1/p-1
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 |
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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 |
---|---|---|
1-Deoxy-D-xylulose 5-phosphate reductoisomerase and plastid isoprenoid biosynthesis during tomato fruit ripening. | 2001 Aug |
|
Biosynthesis of 2-methyl-3-buten-2-ol emitted from needles of Pinus ponderosa via the non-mevalonate DOXP/MEP pathway of isoprenoid formation. | 2001 Jun |
|
Natural abundance carbon isotope composition of isoprene reflects incomplete coupling between isoprene synthesis and photosynthetic carbon flow. | 2003 Apr |
|
Fosmidomycin resistance in adenylate cyclase deficient (cya) mutants of Escherichia coli. | 2003 Sep |
|
Alternative pathways of carotenoid biosynthesis in prokaryotes and eukaryotes. | 2003 Sep-Oct |
|
Biosynthesis of camptothecin. In silico and in vivo tracer study from [1-13C]glucose. | 2004 Jan |
|
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 |
|
Isoprene decreases the concentration of nitric oxide in leaves exposed to elevated ozone. | 2005 May |
|
Evaluation of fosmidomycin analogs as inhibitors of the Synechocystis sp. PCC6803 1-deoxy-D-xylulose 5-phosphate reductoisomerase. | 2006 Apr 1 |
|
Synthesis and biological evaluation of cyclopropyl analogues of fosmidomycin as potent Plasmodium falciparum growth inhibitors. | 2006 Apr 20 |
|
Arylmethyl substituted derivatives of Fosmidomycin: synthesis and antimalarial activity. | 2006 Dec |
|
Involvement of 2-C-methyl-D-erythritol-4-phosphate pathway in biosynthesis of aphidicolin-like tetracyclic diterpene of Scoparia dulcis. | 2006 May |
|
gamma-Substituted bis(pivaloyloxymethyl)ester analogues of fosmidomycin and FR900098. | 2007 Dec |
|
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 |
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
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171792
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66508-37-0
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DBSALT002936
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DTXSID10216711
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IYI1EW66CX
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m5554
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PRIMARY | Merck Index |
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD