FOSTRIECIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H27O9P
Molecular Weight	430.386
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	4
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@](O)(\C=C\[C@H]1CC=CC(=O)O1)[C@@H](C[C@@H](O)\C=C/C=C\C=C\CO)OP(O)(O)=O

InChI

InChIKey=ZMQRJWIYMXZORG-DSWNLJKISA-N

InChI=1S/C19H27O9P/c1-19(23,12-11-16-9-7-10-18(22)27-16)17(28-29(24,25)26)14-15(21)8-5-3-2-4-6-13-20/h2-8,10-12,15-17,20-21,23H,9,13-14H2,1H3,(H2,24,25,26)/b3-2-,6-4+,8-5-,12-11+/t15-,16+,17+,19+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10070885 | https://www.ncbi.nlm.nih.gov/pubmed/9714542

Fostriecin, an antitumor antibiotic produced by Streptomyces pulveraceus, is a strong inhibitor of serine/threonine protein phosphatases type 2A and type 4, and inhibits the catalytic activity of partially purified Topo II (type II topoisomerase) in a non-competitive manner.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform 7 Target ID: P67775 Gene ID: 5515.0 Gene Symbol: PPP2CA Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9373158	Inhibitor 8297	3.2 nM [IC50]
Serine/threonine-protein phosphatase 4 catalytic subunit 2 Target ID: P60510 Gene ID: 5531.0 Gene Symbol: PPP4C Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/9714542	Inhibitor 8297	3.0 nM [IC50]
DNA topoisomerase 2-alpha 2 Target ID: P11388\|\|\|Q9UQP9 Gene ID: 7153.0 Gene Symbol: TOP2A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/2847752	Inhibitor 8297	110.0 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10070885	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
6.354 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10070885	20 mg/m² 1 times / day single, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		FOSTRIECIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
9.965 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10070885	20 mg/m² 1 times / day single, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		FOSTRIECIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.76 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10070885	20 mg/m² 1 times / day single, intravenous dose: 20 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		FOSTRIECIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
47 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 47 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 47 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14739664 Page: p.163	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/14739664 Page: p.163	DLT: Fainting, Hypotension... Dose limiting toxicities: Fainting (grade 3, 25%) Hypotension (grade 1, 25%) Blood creatinine increased (grade 2, 25%) Sources: https://pubmed.ncbi.nlm.nih.gov/14739664 Page: p.163
20 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10070885	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/10070885	DLT: ALT increased... Disc. AE: Oedema, Hypoalbuminaemia... Dose limiting toxicities: ALT increased (25%) AEs leading to discontinuation/dose reduction: Oedema (grade 2, 25%) Hypoalbuminaemia (grade 2, 25%) Proteinuria (25%) Sources: https://pubmed.ncbi.nlm.nih.gov/10070885

AEs

AE	Significance	Dose	Population
Hypotension	grade 1, 25% DLT	47 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 47 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 47 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14739664 Page: p.163	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/14739664 Page: p.163
Blood creatinine increased	grade 2, 25% DLT	47 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 47 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 47 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14739664 Page: p.163	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/14739664 Page: p.163
Fainting	grade 3, 25% DLT	47 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 47 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 47 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14739664 Page: p.163	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/14739664 Page: p.163
ALT increased	25% DLT	20 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10070885	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/10070885
Proteinuria	25% Disc. AE	20 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10070885	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/10070885
Hypoalbuminaemia	grade 2, 25% Disc. AE	20 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10070885	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/10070885
Oedema	grade 2, 25% Disc. AE	20 mg/m2 1 times / day multiple, intravenous Studied dose Dose: 20 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10070885	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/10070885

Sourcing

Vendor/Aggregator	ID	URL
Cayman Chemical	14749	http://www.caymanchem.com/app/template/Product.vm/catalog/14749
Compound Cloud	16759606
Compound Cloud	6913994
Tocris	1840	https://www.tocris.com/search.php?Type=QuickSearch&Value=1840
eMolecules	36550750	https://orderbb.emolecules.com/search/#?query=36550750
eMolecules	76745947	https://orderbb.emolecules.com/search/#?query=76745947
eMolecules	76745948	https://orderbb.emolecules.com/search/#?query=76745948

PubMed

Title	Date	PubMed
Stereospecific Formation of E- and Z-Disubstituted Double Bonds by Dehydratase Domains from Modules 1 and 2 of the Fostriecin Polyketide Synthase.	2017 Oct 11	28902510

Patents

Sample Use Guides

In Vivo Use Guide

Fostriecin was administered intravenously over 60 min on days 1-5 at 4-week intervals. Dose was escalated from 2 mg m(-2) day(-1) to 20 mg m(-2) day(-1) in 20 patients.

Route of Administration: Intravenous

In Vitro Use Guide

Fostriecin pretreatment significantly attenuated the inhibitory effects of salbutamol. For that was investigated the effects of fostriecin on the inhibition of histamine release from HLMC, on β-adrenoceptor-driven responses in mast cells and on desensitization. Long-term incubation (24 h) of mast cells with fostriecin (10-6 M) resulted in a significant (p < 0.001) reduction in the maximal response (from 41.2 [± 3.0] to 29.9 [± 4.2] %) to salbutamol following fostriecin treatment.

Name

Type

Language

FOSTRIECIN

Official Name

English

2H-PYRAN-2-ONE, 5,6-DIHYDRO-6-((1E,3R,4R,6R,7Z,9Z,11E)-3,6,13-TRIHYDROXY-3-METHYL-4-(PHOSPHONOOXY)-1,7,9,11-TRIDECATETRAEN-1-YL)-, (6R)-

Systematic Name

English

PHOSPHOTRIENIN

Common Name

English

fostriecin [INN]

Common Name

English

(6R)-5,6-DIHYDRO-6-((1E,3R,4R,6R,7Z,9Z,11E)-3,6,13-TRIHYDROXY-3-METHYL-4-(PHOSPHONOOXY)-1,7,9,11-TRIDECATETRAENYL)-2H-PYRAN-2-ONE

Systematic Name

English

(+)-FOSTRIECIN

Common Name

English

CL 1565A

Code

English

Fostriecin [WHO-DD]

Common Name

English

NSC-339638

Code

English

CL-1565A

Code

English

2H-PYRAN-2-ONE, 5,6-DIHYDRO-6-((1E,3R,4R,6R,7Z,9Z,11E)-3,6,13-TRIHYDROXY-3-METHYL-4-(PHOSPHONOOXY)-1,7,9,11-TRIDECATETRAENYL)-, (6R)-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1968