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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
Structure of FOSMIDOMYCIN SODIUM

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

HIDE SMILES / InChI

Molecular Formula C4H9NO5P
Molecular Weight 182.0917
Charge -1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
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
Synthesis and biological evaluation with plant cells of new fosmidomycin analogues containing a benzoxazolone or oxazolopyridinone ring.
2004 Dec
Molecular cloning and functional expression of geranylgeranyl pyrophosphate synthase from Coleus forskohlii Briq.
2004 Nov 18
[Effects of fosmidomycin and lovastatin treatment on taxol biosynthesis in suspension culture cells of Taxus chinensis].
2005 Apr
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
Characterization of the Arabidopsis clb6 mutant illustrates the importance of posttranscriptional regulation of the methyl-D-erythritol 4-phosphate pathway.
2005 Feb
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
Alkoxycarbonyloxyethyl ester prodrugs of FR900098 with improved in vivo antimalarial activity.
2005 Jul
[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
AFMoC enhances predictivity of 3D QSAR: a case study with DOXP-reductoisomerase.
2005 May 19
Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations.
2005 May 5
[Isoprenoid pigments in representatives of the family Microbacteriaceae].
2005 May-Jun
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
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
Kinetic characterization of Synechocystis sp. PCC6803 1-deoxy-D-xylulose 5-phosphate reductoisomerase mutants.
2006 Feb
An alternative high-performance liquid chromatographic method for determination of clindamycin in plasma.
2006 Jan
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
Isoprenoid biosynthesis in plants - 2C-methyl-D-erythritol-4-phosphate synthase (IspC protein) of Arabidopsis thaliana.
2006 Oct
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
Bioassay for determination of fosmidomycin in plasma and urine: application for pharmacokinetic dose optimisation.
2007 Apr
Molecular epidemiology of malaria in Cameroon. XXV. In vitro activity of fosmidomycin and its derivatives against fresh clinical isolates of Plasmodium falciparum and sequence analysis of 1-deoxy-D-xylulose 5-phosphate reductoisomerase.
2007 Aug
An Escherichia coli undecaprenyl-pyrophosphate phosphatase implicated in undecaprenyl phosphate recycling.
2007 Aug
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
Isoprenoid biosynthesis of the apicoplast as drug target.
2007 Jan
Conformationally restrained aromatic analogues of fosmidomycin and FR900098.
2007 Jul
Structures of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate reductoisomerase provide new insights into catalysis.
2007 Jul 6
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
Plants used traditionally to treat malaria in Brazil: the archives of Flora Medicinal.
2007 May 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
Organocatalytic asymmetric direct phosphonylation of alpha,beta-unsaturated aldehydes: mechanism, scope, and application in synthesis.
2007 Nov 9
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
Gateways to clinical trials.
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
Herbivore-induced terpenoid emission in Medicago truncatula: concerted action of jasmonate, ethylene and calcium signaling.
2008 Jan
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 15:36:53 UTC 2023
Edited
by admin
on Fri Dec 15 15:36:53 UTC 2023
Record UNII
IYI1EW66CX
Record Status Validated (UNII)
Record Version
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Name Type Language
FOSMIDOMYCIN SODIUM
Common Name English
PHOSPHONIC ACID, (3-(FORMYLHYDROXYAMINO)PROPYL)-, MONOSODIUM SALT
Common Name English
FOSMIDOMYCIN MONOSODIUM SALT [MI]
Common Name English
FR-31564
Common Name English
FOSMIDOMYCIN MONOSODIUM SALT
MI  
Common Name English
FOSMIDOMYCIN SODIUM [JAN]
Common Name English
Code System Code Type Description
PUBCHEM
171792
Created by admin on Fri Dec 15 15:36:53 UTC 2023 , Edited by admin on Fri Dec 15 15:36:53 UTC 2023
PRIMARY
CAS
66508-37-0
Created by admin on Fri Dec 15 15:36:53 UTC 2023 , Edited by admin on Fri Dec 15 15:36:53 UTC 2023
PRIMARY
DRUG BANK
DBSALT002936
Created by admin on Fri Dec 15 15:36:53 UTC 2023 , Edited by admin on Fri Dec 15 15:36:53 UTC 2023
PRIMARY
EPA CompTox
DTXSID10216711
Created by admin on Fri Dec 15 15:36:53 UTC 2023 , Edited by admin on Fri Dec 15 15:36:53 UTC 2023
PRIMARY
FDA UNII
IYI1EW66CX
Created by admin on Fri Dec 15 15:36:53 UTC 2023 , Edited by admin on Fri Dec 15 15:36:53 UTC 2023
PRIMARY
MERCK INDEX
m5554
Created by admin on Fri Dec 15 15:36:53 UTC 2023 , Edited by admin on Fri Dec 15 15:36:53 UTC 2023
PRIMARY Merck Index
Related Record Type Details
PARENT -> SALT/SOLVATE