EPOTHILONE A

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H39NO6S
Molecular Weight	493.656
Optical Activity	( - )
Defined Stereocenters	7 / 7
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H]1CCC[C@H]2O[C@H]2C[C@H](OC(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@H]1O)C(\C)=C\C3=CSC(C)=N3

InChI

InChIKey=HESCAJZNRMSMJG-KKQRBIROSA-N

InChI=1S/C26H39NO6S/c1-14-8-7-9-19-21(32-19)11-20(15(2)10-18-13-34-17(4)27-18)33-23(29)12-22(28)26(5,6)25(31)16(3)24(14)30/h10,13-14,16,19-22,24,28,30H,7-9,11-12H2,1-6H3/b15-10+/t14-,16+,19+,20-,21-,22-,24-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19707459
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/7757983

Epothilone A is a natural compound, originally discovered from the myxobacterium Sorangium cellulosum. Epothilones A, a macrolide compound, stabilizes polymerized microtubules, leading to mitotic arrest and cytotoxicity in proliferating cells. While epothilone A shows potent antineoplastic activity in vitro, these effects were not seen in preclinical in vivo models due to its poor metabolic stability and unfavorable pharmacokinetics.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin 69 Target ID: CHEMBL2095182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7757983 \| https://www.ncbi.nlm.nih.gov/pubmed/8999970 \| https://www.ncbi.nlm.nih.gov/pubmed/26986898 \| https://www.ncbi.nlm.nih.gov/pubmed/24524625 \| https://www.ncbi.nlm.nih.gov/pubmed/22731768	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 609 Sources: http://adisinsight.springer.com/drugs/800005848	Primary		Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Characterizing the Epothilone Binding Site on β-Tubulin by Photoaffinity Labeling: Identification of β-Tubulin Peptides TARGSQQY and TSRGSQQY as Targets of an Epothilone Photoprobe for Polymerized Tubulin.	2016-04-14	26986898
Molecular recognition of epothilones by microtubules and tubulin dimers revealed by biochemical and NMR approaches.	2014-04-18	24524625
Induction of apoptosis in human ovarian cancer cells by new anticancer compounds, epothilone A and B.	2013-02	22995584
Comparative binding energy (COMBINE) analysis supports a proposal for the binding mode of epothilones to β-tubulin.	2012-05	22431398
Structural insight into the mechanism of epothilone A bound to beta-tubulin and its mutants at Arg282Gln and Thr274Ile.	2012	22731768
Epothilones and related structures--a new class of microtubule inhibitors with potent in vivo antitumor activity.	2000-05-17	10799747
Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol(R)).	1997-01-24	8999970
Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action.	1995-06-01	7757983

Patents

Sample Use Guides

In Vivo Use Guide

Epothilone A has poor pharmacologic properties with loss of structural stability in animal plasma which led to the agent being dropped from further studies.

Route of Administration: Unknown

In Vitro Use Guide

Epothilone A is cytotoxic to KB3-1, KBV-1, Hela, and Hs578T cells, with EC50 values ranging from 13 nM to 160 nM and induce mitotic arrest in KB3-1, KBV-1, Hela, and Hs578T cells with EC50 values ranging from 7 nM to 170 nM

Name

Type

Language

(-)-EPOTHILONE A

Preferred Name

English

EPOTHILONE A

Common Name

English

EPO A

Common Name

English

EPOTHILONE A [MI]

Common Name

English

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

Systematic Name

English

Epothilone A [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1922