SAGOPILONE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C30H41NO6S
Molecular Weight	543.715
Optical Activity	( - )
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H]1CCC[C@@]2(C)O[C@H]2C[C@H](OC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](CC=C)[C@H]1O)C3=CC=C4SC(C)=NC4=C3

InChI

InChIKey=BFZKMNSQCNVFGM-UCEYFQQTSA-N

InChI=1S/C30H41NO6S/c1-7-9-20-27(34)17(2)10-8-13-30(6)25(37-30)15-22(19-11-12-23-21(14-19)31-18(3)38-23)36-26(33)16-24(32)29(4,5)28(20)35/h7,11-12,14,17,20,22,24-25,27,32,34H,1,8-10,13,15-16H2,2-6H3/t17-,20+,22-,24-,25-,27-,30+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://clinicaltrials.gov/ct2/show/NCT00246688 | https://clinicaltrials.gov/ct2/show/NCT00397072 | https://www.ncbi.nlm.nih.gov/pubmed/23522488 | https://www.ncbi.nlm.nih.gov/pubmed/18593931

Sagopilone (BAY86-5302; ZK 219477; ZK-EPO) is a synthetic epothilone, an analog of patupilone that was developed by Bayer HealthCare as an anticancer agent. Epothilones are 16-member ring macrolides have demonstrated potent antiproliferative activity in several different multidrug-resistant and paclitaxel-resistant tumor cell lines in vitro and in vivo. Sagopilone binds to tubulin and induces microtubule polymerization, which may result in the induction of G2/M arrest, and apoptosis. Sagopilone is not a substrate for the P-glycoprotein efflux pump and so may exhibit activity in multidrug-resistant tumors. This drug was studied in clinical trials phase II in patients with recurrent ovarian cancer, in metastatic melanoma patients, for the treatment of advanced stage breast cancer and in the treatment of Glioblastoma patients. However, the development of this drug was discontinued, because of its adverse effects, including peripheral neuropathy.

CNS Activity

Approval Year

PubMed

Title	Date	PubMed
Exon array analysis using re-defined probe sets results in reliable identification of alternatively spliced genes in non-small cell lung cancer.	2010-11-30	21118496
Phase II trial of sagopilone, a novel epothilone analog in metastatic melanoma.	2010-11-09	20924376
Phase II study evaluating the efficacy and safety of sagopilone (ZK-EPO) in patients with metastatic breast cancer that has progressed following chemotherapy.	2010-10	20697802
Treatment of cutaneous melanoma: current approaches and future prospects.	2010-08-17	21188111
Polymeric micelles for parenteral delivery of sagopilone: physicochemical characterization, novel formulation approaches and their toxicity assessment in vitro as well as in vivo.	2010-06	20188169
Non-ionic dendritic glycerol-based amphiphiles: novel excipients for the solubilization of poorly water-soluble anticancer drug Sagopilone.	2010-04-16	20188825
Solubilization of sagopilone, a poorly water-soluble anticancer drug, using polymeric micelles for parenteral delivery.	2010-04-15	20100557
Gateways to clinical trials.	2010-04-13	20383346
Comparative profiling of the novel epothilone, sagopilone, in xenografts derived from primary non-small cell lung cancer.	2010-03-01	20179216
Phase I study of the novel, fully synthetic epothilone sagopilone (ZK-EPO) in patients with solid tumors.	2010-03	19880436
Improving the ex vivo stability of drug ester compounds in rat and dog serum: inhibition of the specific esterases and implications on their identity.	2010-02-05	19850433
Sagopilone, a microtubule stabilizer for the potential treatment of cancer.	2009-12	19943207
Weekly administration of sagopilone (ZK-EPO), a fully synthetic epothilone, in patients with refractory solid tumours: results of a phase I trial.	2009-10-20	19773753
Systemic sagopilone (ZK-EPO) treatment of patients with recurrent malignant gliomas.	2009-10	19381446
Management of advanced breast cancer with the epothilone B analog, ixabepilone.	2009-09-21	19920932
The epothilones: how pharmacology relates to clinical utility.	2009-07	19584389
Sagopilone inhibits breast cancer bone metastasis and bone destruction due to simultaneous inhibition of both tumor growth and bone resorption.	2009-06-01	19470728
Gateways to clinical trials.	2009-06	19649342
Sagopilone crosses the blood-brain barrier in vivo to inhibit brain tumor growth and metastases.	2009-04	18780814
Novel microtubule-targeting agents - the epothilones.	2008-12	19707459
Gateways to Clinical Trials.	2008-11	19229381
Sagopilone (ZK-EPO): from a natural product to a fully synthetic clinical development candidate.	2008-11	18922109
Novel therapies in genitourinary cancer: an update.	2008-08-11	18694493
Improved cellular pharmacokinetics and pharmacodynamics underlie the wide anticancer activity of sagopilone.	2008-07-01	18593931
New therapeutic options for chemotherapy-resistant metastatic breast cancer: the epothilones.	2008	18197722

Patents

Sample Use Guides

In Vivo Use Guide

Subjects received one infusion (for 0.5 h) of sagopilone every 3 weeks at a dose of 16 mg/m2 (maximum up to 32 mg) for approximately 18 weeks. 10.5 mg lyophilized sagopilone per vial

Route of Administration: Intravenous

Name

Type

Language

(1S,3S,7S,10R,11S,12S,16R)-10-ALLYL-7,11-DIHYDROXY-8,8,12,16-TETRAMETHYL-3-(2-METHYL-1,3-BENZOTHIAZOL-5-YL)-4,17-DIOXABICYCLO(14.1.0)HEPTADECANE-5,9-DIONE

Preferred Name

English

SAGOPILONE

Official Name

English

(1S,3S,7S,10R,11S,12S,16R)-10-ALLYL-7,11-DIHYDROXY-8,8,12,16-TETRAMETHYL-3-(2-METHYLBENZOTHIAZOL-5-YL)-4,17-DIOXABICYCLO(14.1.0)HEPTADECANE-5,9-DIONE

Systematic Name

English

DE-03757

Code

English

4,17-DIOXABICYCLO(14.1.0)HEPTADECANE-5,9-DIONE, 7,11-DIHYDROXY-8,8,12,16-TETRAMETHYL-3-(2-METHYL-5-BENZOTHIAZOLYL)-10-(2-PROPENYL)-, (1S,3S,7S,10R,11S,12S,16R)-

Common Name

English

ZK-219477

Code

English

Sagopilone [WHO-DD]

Common Name

English

ZK-EPO

Code

English

(1S,3S,7S,10R,11S,12S,16R)-7,11-DIHYDROXY-8,8,12,16-TETRAMETHYL-3-(2-METHYL-1,3- BENZOTHIAZOL-5-YL)-10-(PROP-2-ENYL)-4,17-DIOXABICYCLO(14.1.0)HEPTADECANE-5,9-DIONE

Common Name

English

SAGOPILONE [USAN]

Common Name

English

ZK219477

Code

English

sagopilone [INN]

Common Name

English

BAY86-5302

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C67437