FOSMIDOMYCIN SODIUM

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 Search

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

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 8297		28.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Malaria 95 Sources: https://clinicaltrials.gov/ct2/show/NCT00214643	Primary		Phase III 656	Unknown Approved Use Unknown
Urinary tract infections 205 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12937969	Primary		Phase II 1132	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
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	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

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
1.87 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

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
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
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

PubMed

Title	Date	PubMed
1-Deoxy-D-xylulose 5-phosphate reductoisomerase and plastid isoprenoid biosynthesis during tomato fruit ripening.	2001 Aug	11532167
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	11469599
Natural abundance carbon isotope composition of isoprene reflects incomplete coupling between isoprene synthesis and photosynthetic carbon flow.	2003 Apr	12692331
Fosmidomycin resistance in adenylate cyclase deficient (cya) mutants of Escherichia coli.	2003 Sep	14519998
Alternative pathways of carotenoid biosynthesis in prokaryotes and eukaryotes.	2003 Sep-Oct	15255207
Biosynthesis of camptothecin. In silico and in vivo tracer study from [1-13C]glucose.	2004 Jan	14657405
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	15567415
[Prevalence of nonmevalonate and mevalonate pathways for isoprenoid biosynthesis among bacteria of different systematic groups].	2005 Mar-Apr	15938394
Isoprene decreases the concentration of nitric oxide in leaves exposed to elevated ozone.	2005 May	15819906
Evaluation of fosmidomycin analogs as inhibitors of the Synechocystis sp. PCC6803 1-deoxy-D-xylulose 5-phosphate reductoisomerase.	2006 Apr 1	16310360
Synthesis and biological evaluation of cyclopropyl analogues of fosmidomycin as potent Plasmodium falciparum growth inhibitors.	2006 Apr 20	16610809
Arylmethyl substituted derivatives of Fosmidomycin: synthesis and antimalarial activity.	2006 Dec	17055117
Involvement of 2-C-methyl-D-erythritol-4-phosphate pathway in biosynthesis of aphidicolin-like tetracyclic diterpene of Scoparia dulcis.	2006 May	16651787
gamma-Substituted bis(pivaloyloxymethyl)ester analogues of fosmidomycin and FR900098.	2007 Dec	17994605
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	18421757

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

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

Common Name

English

FOSMIDOMYCIN SODIUM [JAN]

Common Name

English

Code System Code Type Description

PUBCHEM

171792