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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
Structure of FOSMIDOMYCIN

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)

HIDE SMILES / InChI

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

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: O96693
Gene ID: NA
Gene Symbol: DXR
Target Organism: Plasmodium falciparum (isolate HB3)
28.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4.58 μg/mL
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
27.67 μg × h/mL
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
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
0.5 h
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
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
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
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

Funbound

ValueDoseCo-administeredAnalytePopulation
99%
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

PubMed

TitleDatePubMed
Isoprene produced by leaves protects the photosynthetic apparatus against ozone damage, quenches ozone products, and reduces lipid peroxidation of cellular membranes.
2001 Dec
E. coli MEP synthase: steady-state kinetic analysis and substrate binding.
2002 Jan 8
Antisense and chemical suppression of the nonmevalonate pathway affects ent-kaurene biosynthesis in Arabidopsis.
2002 Jun
On-line analysis of the (13)CO(2) labeling of leaf isoprene suggests multiple subcellular origins of isoprene precursors.
2002 Oct
Natural abundance carbon isotope composition of isoprene reflects incomplete coupling between isoprene synthesis and photosynthetic carbon flow.
2003 Apr
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
High-throughput screen for inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase by surrogate ligand competition.
2003 Jun
Structural basis of fosmidomycin action revealed by the complex with 2-C-methyl-D-erythritol 4-phosphate synthase (IspC). Implications for the catalytic mechanism and anti-malaria drug development.
2003 May 16
Role of the non-mevalonate pathway in indole alkaloid production by Catharanthus roseus hairy roots.
2003 May-Jun
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
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
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
Induction of de novo volatile terpene biosynthesis via cytosolic and plastidial pathways by methyl jasmonate in foliage of Vitis vinifera L.
2005 Apr 6
Fosmidomycin analogues as inhibitors of monoterpenoid indole alkaloid production in Catharanthus roseus cells.
2005 Aug
Bacterial genome adaptation to niches: divergence of the potential virulence genes in three Burkholderia species of different survival strategies.
2005 Dec 7
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
AFMoC enhances predictivity of 3D QSAR: a case study with DOXP-reductoisomerase.
2005 May 19
The Arabidopsis csb3 mutant reveals a regulatory link between salicylic acid-mediated disease resistance and the methyl-erythritol 4-phosphate pathway.
2005 Oct
A fragment-based approach to understanding inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase.
2005 Oct
The capacity for thermal protection of photosynthetic electron transport varies for different monoterpenes in Quercus ilex.
2005 Sep
Synthesis and biological evaluation of cyclopropyl analogues of fosmidomycin as potent Plasmodium falciparum growth inhibitors.
2006 Apr 20
The relationship between the methyl-erythritol phosphate pathway leading to emission of volatile isoprenoids and abscisic acid content in leaves.
2006 Aug
Dynamic pathway allocation in early terpenoid biosynthesis of stress-induced lima bean leaves.
2006 Aug
Arylmethyl substituted derivatives of Fosmidomycin: synthesis and antimalarial activity.
2006 Dec
Isoprenoid biosynthesis as a drug target: bisphosphonate inhibition of Escherichia coli K12 growth and synergistic effects of fosmidomycin.
2006 Dec 14
An alternative high-performance liquid chromatographic method for determination of clindamycin in plasma.
2006 Jan
Plastid cues posttranscriptionally regulate the accumulation of key enzymes of the methylerythritol phosphate pathway in Arabidopsis.
2006 May
Enhanced flux through the methylerythritol 4-phosphate pathway in Arabidopsis plants overexpressing deoxyxylulose 5-phosphate reductoisomerase.
2006 Nov
Isoprenoid biosynthesis in plants - 2C-methyl-D-erythritol-4-phosphate synthase (IspC protein) of Arabidopsis thaliana.
2006 Oct
Bioassay for determination of fosmidomycin in plasma and urine: application for pharmacokinetic dose optimisation.
2007 Apr
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
Evidence of artemisinin production from IPP stemming from both the mevalonate and the nonmevalonate pathways.
2007 Dec
Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum.
2007 Jun
Pharmacokinetics and pharmacodynamics of fosmidomycin monotherapy and combination therapy with clindamycin in the treatment of multidrug resistant falciparum malaria.
2007 May 25
The structure of Mycobacteria 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase, an essential enzyme, provides a platform for drug discovery.
2007 Oct 23
Assessment of in vitro antimalarial interactions between dihydroartemisinin and fosmidomycin.
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
Synthesis of beta- and gamma-oxa isosteres of fosmidomycin and FR900098 as antimalarial candidates.
2008 Mar 15
Patents

Sample Use Guides

Fosmidomycin-clindamycin (30 mg/kg and 10 mg/kg) given twice daily for three days
Route of Administration: Oral
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 Wed Jul 05 23:15:26 UTC 2023
Edited
by admin
on Wed Jul 05 23:15:26 UTC 2023
Record UNII
5829E3D9I9
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FOSMIDOMYCIN
INN   MART.   MI  
INN  
Official Name English
fosmidomycin [INN]
Common Name English
FOSMIDOMYCIN [MART.]
Common Name English
FOSMIDOMYCIN [MI]
Common Name English
(3-(N-HYDROXYFORMAMIDO)PROPYL)PHOSPHONIC ACID
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C258
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
Code System Code Type Description
CAS
66508-53-0
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
ChEMBL
CHEMBL203125
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
WIKIPEDIA
FOSMIDOMYCIN
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
EPA CompTox
DTXSID70216712
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
CHEBI
443725
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
NCI_THESAURUS
C65764
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
EVMPD
SUB07802MIG
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
INN
5104
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
FDA UNII
5829E3D9I9
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
MERCK INDEX
M5554
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY Merck Index
MESH
C024640
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
DRUG BANK
DB02948
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
SMS_ID
100000080441
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
PUBCHEM
572
Created by admin on Wed Jul 05 23:15:26 UTC 2023 , Edited by admin on Wed Jul 05 23:15:26 UTC 2023
PRIMARY
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