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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 of EPOTHILONE A

SMILES

[H][C@@]12CCC[C@H](C)[C@H](O)[C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O[C@@H](C[C@]1([H])O2)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
Molecular Formula C26H39NO6S
Molecular Weight 493.656
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 7 / 7
E/Z Centers 1
Optical Activity UNSPECIFIED

Description
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

Merck
216
Curator's Comment: # Merck & Co

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Basic research
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action.
1995 Jun 1
Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol(R)).
1997 Jan 24
Structural insight into the mechanism of epothilone A bound to beta-tubulin and its mutants at Arg282Gln and Thr274Ile.
2012
Comparative binding energy (COMBINE) analysis supports a proposal for the binding mode of epothilones to β-tubulin.
2012 May
Induction of apoptosis in human ovarian cancer cells by new anticancer compounds, epothilone A and B.
2013 Feb
Molecular recognition of epothilones by microtubules and tubulin dimers revealed by biochemical and NMR approaches.
2014 Apr 18
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 Apr 14
Patents

Patents

06399638
2
06441186
1
06605599
2
06800653
2
07067544
1
07125899
2
07241755
2
07317100
1
08536327
2
JP2001503785A
3
JP2002530107A
5
JP2005068156A
2
JP2007508039A
114
JP2007509861A
8
JP2008539832A
82
JP2009525790A
101
JP2011173928A
2
JP3287852B2
2
JP4523843B2
2
JP4662635B2
4
JP4758474B2
87
JP4776843B2
17

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
Substance Class Chemical
Created
by admin
on Sat Dec 16 10:09:19 GMT 2023
Edited
by admin
on Sat Dec 16 10:09:19 GMT 2023
Record UNII
51E07YBX96
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
EPOTHILONE A
MI   WHO-DD  
Common 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
Created by admin on Sat Dec 16 10:09:19 GMT 2023 , Edited by admin on Sat Dec 16 10:09:19 GMT 2023
NCI_THESAURUS C67437
Created by admin on Sat Dec 16 10:09:19 GMT 2023 , Edited by admin on Sat Dec 16 10:09:19 GMT 2023
Code System Code Type Description
CHEBI
31549
Created by admin on Sat Dec 16 10:09:19 GMT 2023 , Edited by admin on Sat Dec 16 10:09:19 GMT 2023
PRIMARY
SMS_ID
100000177892
Created by admin on Sat Dec 16 10:09:19 GMT 2023 , Edited by admin on Sat Dec 16 10:09:19 GMT 2023
PRIMARY
CAS
186692-57-9
Created by admin on Sat Dec 16 10:09:19 GMT 2023 , Edited by admin on Sat Dec 16 10:09:19 GMT 2023
SUPERSEDED
FDA UNII
51E07YBX96
Created by admin on Sat Dec 16 10:09:19 GMT 2023 , Edited by admin on Sat Dec 16 10:09:19 GMT 2023
PRIMARY
PUBCHEM
448799
Created by admin on Sat Dec 16 10:09:19 GMT 2023 , Edited by admin on Sat Dec 16 10:09:19 GMT 2023
PRIMARY
MERCK INDEX
m4954
Created by admin on Sat Dec 16 10:09:19 GMT 2023 , Edited by admin on Sat Dec 16 10:09:19 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID10332288
Created by admin on Sat Dec 16 10:09:19 GMT 2023 , Edited by admin on Sat Dec 16 10:09:19 GMT 2023
PRIMARY
NCI_THESAURUS
C1622
Created by admin on Sat Dec 16 10:09:19 GMT 2023 , Edited by admin on Sat Dec 16 10:09:19 GMT 2023
PRIMARY
CAS
152044-53-6
Created by admin on Sat Dec 16 10:09:19 GMT 2023 , Edited by admin on Sat Dec 16 10:09:19 GMT 2023
PRIMARY
NIH
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