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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
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
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 Fri Dec 15 15:46:57 GMT 2023
Edited
by admin
on Fri Dec 15 15:46:57 GMT 2023
Record UNII
5829E3D9I9
Record Status Validated (UNII)
Record Version
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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 Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
Code System Code Type Description
CAS
66508-53-0
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
ChEMBL
CHEMBL203125
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
WIKIPEDIA
FOSMIDOMYCIN
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
EPA CompTox
DTXSID70216712
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
CHEBI
443725
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
NCI_THESAURUS
C65764
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
EVMPD
SUB07802MIG
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
INN
5104
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
FDA UNII
5829E3D9I9
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
MERCK INDEX
m5554
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY Merck Index
MESH
C024640
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
DRUG BANK
DB02948
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
SMS_ID
100000080441
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
PUBCHEM
572
Created by admin on Fri Dec 15 15:46:57 GMT 2023 , Edited by admin on Fri Dec 15 15:46:57 GMT 2023
PRIMARY
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