FOSMIDOMYCIN

Investigational

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 Search

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
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
1-deoxy-D-xylulose 5-phosphate reductoisomerase, apicoplastic 2 Target ID: O96693 Gene ID: NA Gene Symbol: DXR Target Organism: Plasmodium falciparum (isolate HB3) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12937969	Inhibitor 8504		28.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Malaria 96 Sources: https://clinicaltrials.gov/ct2/show/NCT00214643	Primary		Phase III 665	Unknown Approved Use Unknown
Urinary tract infections 207 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12937969	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	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
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
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

AUC

Value	Dose	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
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
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

T_1/2

Value	Dose	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
1.58 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
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

F_unbound

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

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	R980	https://aksci.com/item_detail.php?cat=R980
ApexBio Technology	C4898	https://www.apexbt.com/catalogsearch/result/?q=C4898
BOC Sciences	66508-53-0	http://www.bocsci.com/description.asp?cas=66508-53-0
Cayman Chemical	16000	http://www.caymanchem.com/app/template/Product.vm/catalog/16000
Chemspace	CSC000076817	https://chem-space.com/CSC000076817
eMolecules	300143136	https://orderbb.emolecules.com/search/#?query=300143136
eMolecules	50153329	https://orderbb.emolecules.com/search/#?query=50153329
eMolecules	8321444	https://orderbb.emolecules.com/search/#?query=8321444
Enamine	BBV-38278542	http://www.enaminestore.com/catalog/BBV-38278542
MuseChem	I006850	https://www.musechem.com/product/I006850.html
Toronto Research Chemicals	C176670	https://www.trc-canada.com/product-detail/?CatNum=C176670
Toronto Research Chemicals	F728500	https://www.trc-canada.com/product-detail/?CatNum=F728500

PubMed

Title	Date	PubMed
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.	2008-04	18421757
Significance of terpenoids in induced indirect plant defence against herbivorous arthropods.	2008-04	18208515
Synthesis of beta- and gamma-oxa isosteres of fosmidomycin and FR900098 as antimalarial candidates.	2008-03-15	18158249
Herbivore-induced terpenoid emission in Medicago truncatula: concerted action of jasmonate, ethylene and calcium signaling.	2008-01	17924138
gamma-Substituted bis(pivaloyloxymethyl)ester analogues of fosmidomycin and FR900098.	2007-12	17994605
Evidence of artemisinin production from IPP stemming from both the mevalonate and the nonmevalonate pathways.	2007-12	17710406
Organocatalytic asymmetric direct phosphonylation of alpha,beta-unsaturated aldehydes: mechanism, scope, and application in synthesis.	2007-11-09	17927255
The structure of Mycobacteria 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase, an essential enzyme, provides a platform for drug discovery.	2007-10-23	17956607
Synthesis and evaluation of alpha,beta-unsaturated alpha-aryl-substituted fosmidomycin analogues as DXR inhibitors.	2007-09-01	17583502
Assessment of in vitro antimalarial interactions between dihydroartemisinin and fosmidomycin.	2007-09	18041293
Gateways to clinical trials.	2007-09	17982511
Novel deoxyxylulosephosphate-reductoisomerase inhibitors: fosmidomycin derivatives with spacious acyl residues.	2007-09	17806130
Elicitor induced activation of the methylerythritol phosphate pathway toward phytoalexins biosynthesis in rice.	2007-09	17634747
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.	2007-08	17690389
An Escherichia coli undecaprenyl-pyrophosphate phosphatase implicated in undecaprenyl phosphate recycling.	2007-08	17660416
The methylerythritol phosphate pathway for isoprenoid biosynthesis in coccidia: presence and sensitivity to fosmidomycin.	2007-08	17399705
Structures of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate reductoisomerase provide new insights into catalysis.	2007-07-06	17491006
Conformationally restrained aromatic analogues of fosmidomycin and FR900098.	2007-07	17611943
Structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in a quaternary complex with a magnesium ion, NADPH and the antimalarial drug fosmidomycin.	2007-06-01	17554164
Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum.	2007-06	17568945
Pharmacokinetics and pharmacodynamics of fosmidomycin monotherapy and combination therapy with clindamycin in the treatment of multidrug resistant falciparum malaria.	2007-05-25	17531088
Divergent strategy for the synthesis of alpha-aryl-substituted fosmidomycin analogues.	2007-05-11	17428097
Plants used traditionally to treat malaria in Brazil: the archives of Flora Medicinal.	2007-05-01	17472740
Bioassay for determination of fosmidomycin in plasma and urine: application for pharmacokinetic dose optimisation.	2007-04	17258829
Isoprenoid biosynthesis of the apicoplast as drug target.	2007-01	17266527
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	17430177
Isoprenoid biosynthesis as a drug target: bisphosphonate inhibition of Escherichia coli K12 growth and synergistic effects of fosmidomycin.	2006-12-14	17149863
Arylmethyl substituted derivatives of Fosmidomycin: synthesis and antimalarial activity.	2006-12	17055117
Enhanced flux through the methylerythritol 4-phosphate pathway in Arabidopsis plants overexpressing deoxyxylulose 5-phosphate reductoisomerase.	2006-11	16941216
Isoprenoid biosynthesis in plants - 2C-methyl-D-erythritol-4-phosphate synthase (IspC protein) of Arabidopsis thaliana.	2006-10	16972937
Synthesis and antimalarial activity of chain substituted pivaloyloxymethyl ester analogues of Fosmidomycin and FR900098.	2006-08-01	16679022
The relationship between the methyl-erythritol phosphate pathway leading to emission of volatile isoprenoids and abscisic acid content in leaves.	2006-08	16766667
Dynamic pathway allocation in early terpenoid biosynthesis of stress-induced lima bean leaves.	2006-08	16580034
Involvement of 2-C-methyl-D-erythritol-4-phosphate pathway in biosynthesis of aphidicolin-like tetracyclic diterpene of Scoparia dulcis.	2006-05	16651787
Plastid cues posttranscriptionally regulate the accumulation of key enzymes of the methylerythritol phosphate pathway in Arabidopsis.	2006-05	16531478
Synthesis and biological evaluation of cyclopropyl analogues of fosmidomycin as potent Plasmodium falciparum growth inhibitors.	2006-04-20	16610809
Synthesis of alpha-substituted fosmidomycin analogues as highly potent Plasmodium falciparum growth inhibitors.	2006-04-01	16439126
Evaluation of fosmidomycin analogs as inhibitors of the Synechocystis sp. PCC6803 1-deoxy-D-xylulose 5-phosphate reductoisomerase.	2006-04-01	16310360
Kinetic characterization of Synechocystis sp. PCC6803 1-deoxy-D-xylulose 5-phosphate reductoisomerase mutants.	2006-02	16219495
An alternative high-performance liquid chromatographic method for determination of clindamycin in plasma.	2006-01	16771232
Bacterial genome adaptation to niches: divergence of the potential virulence genes in three Burkholderia species of different survival strategies.	2005-12-07	16336651
The Arabidopsis csb3 mutant reveals a regulatory link between salicylic acid-mediated disease resistance and the methyl-erythritol 4-phosphate pathway.	2005-10	16167903
A fragment-based approach to understanding inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase.	2005-10	16116659
The capacity for thermal protection of photosynthetic electron transport varies for different monoterpenes in Quercus ilex.	2005-09	16126854
[Isoprenoid pigments in representatives of the family Microbacteriaceae].	2005-08-27	16119846
Fosmidomycin analogues as inhibitors of monoterpenoid indole alkaloid production in Catharanthus roseus cells.	2005-08	16054176
Alkoxycarbonyloxyethyl ester prodrugs of FR900098 with improved in vivo antimalarial activity.	2005-07	15996004
[Prevalence of nonmevalonate and mevalonate pathways for isoprenoid biosynthesis among bacteria of different systematic groups].	2005-06-09	15938394
AFMoC enhances predictivity of 3D QSAR: a case study with DOXP-reductoisomerase.	2005-05-19	15887963
The plastid of Plasmodium spp.: a target for inhibitors.	2005	16265894

Patents

Sample Use Guides

In Vivo Use Guide

Fosmidomycin-clindamycin (30 mg/kg and 10 mg/kg) given twice daily for three days

Route of Administration: Oral

In Vitro Use Guide

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 `Mon Mar 31 18:08:26 GMT 2025` Edited by `admin` on `Mon Mar 31 18:08:26 GMT 2025`
Record UNII	5829E3D9I9
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

FOSMIDOMYCIN

Official Name

English

FOSMIDOMYCIN [MI]

Preferred Name

English

fosmidomycin [INN]

Common Name

English

FOSMIDOMYCIN [MART.]

Common Name

English

(3-(N-HYDROXYFORMAMIDO)PROPYL)PHOSPHONIC ACID

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C258