Epothilone A

Names

[ CAS No. ]:
152044-53-6

[ Name ]:
Epothilone A

[Synonym ]:
UNII-51E07YBX96
Epothilone A
(-)-Epothilone A
Epo A
4,17-Dioxabicyclo[14.1.0]heptadecane-5,9-dione, 7,11-dihydroxy-8,8,10,12-tetramethyl-3-[(E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-, (1S,3S,7S,10R,11S,12S,16R)-
[1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]-7,11-dihydroxy-8,8,10,12-tetramethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
Epothilon A
(1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12-tetramethyl-3-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
(1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-8,8,10,12-tetramethyl-3-[(1E)-1-(2-methyl-1,3-thiazol-4-yl)-1-propen-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
4,17-Dioxabicyclo[14.1.0]heptadecane-5,9-dione, 7,11-dihydroxy-8,8,10,12-tetramethyl-3-[(E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-, (1R,3R,7R,10S,11R,12R,16S)-
(1R,3R,7R,10S,11R,12R,16S)-7,11-Dihydroxy-8,8,10,12-tetramethyl-3-[(1E)-1-(2-methyl-1,3-thiazol-4-yl)-1-propen-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
epithilone A
Epothilones
(1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12-tetramethyl-3-[(1E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione

Biological Activity

[Description]:

Epothilone A is a competitive inhibitor of the binding of [3H] paclitaxel to tubulin polymers, with a Ki of 0.6-1.4 μM.

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Research Areas >> Cancer

Natural Products >> Others

[In Vitro]

Epothilone A is a competitive inhibitor of the binding of [3H] paclitaxel to tubulin polymers. The apparent Ki value for Epothilone A is 1.4 μM by Hanes analysis and 0.6 μM by Dixon analysis[1]. Epothilone A, is noted to be highly cytotoxic (IC50=0.05 μM) in vitro when applied to the human T-24 bladder carcinoma cell line. The binding affinity of Epothilone A to tubulin is of the same order of magnitude as the binding affinity of paclitaxel to tubulin based on competition assays. The IC50 for displacement of 100 nM of (3H) paclitaxel from the tubulin binding site is 3.6 μM for paclitaxel, 2.3 μM for Epothilone A, and 3.3 μM for patupilone[2].

[References]

[1]. Kowalski RJ, et al. Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol(R)). J Biol Chem. 1997 Jan 24;272(4):2534-41.

[2]. Cheng KL, et al. Novel microtubule-targeting agents - the epothilones. Biologics. 2008 Dec;2(4):789-811.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
683.3±55.0 °C at 760 mmHg

[ Melting Point ]:
95ºC

[ Molecular Formula ]:
C₂₆H₃₉NO₆S

[ Molecular Weight ]:
493.656

[ Flash Point ]:
367.1±31.5 °C

[ Exact Mass ]:
493.249817

[ PSA ]:
137.49000

[ LogP ]:
2.54

[ Vapour Pressure ]:
0.0±2.2 mmHg at 25°C

[ Index of Refraction ]:
1.532

[ Storage condition ]:
-20°C

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Identifying off-target effects and hidden phenotypes of drugs in human cells.

Nat. Chem. Biol. 2 , 329-37, (2006)

We present a strategy for identifying off-target effects and hidden phenotypes of drugs by directly probing biochemical pathways that underlie therapeutic or toxic mechanisms in intact, living cells. ...

Neuronal transcriptional repressor REST suppresses an Atoh7-independent program for initiating retinal ganglion cell development.

Dev. Biol. 349 , 90-9, (2011)

As neuronal progenitors differentiate into neurons, they acquire a unique set of transcription factors. The transcriptional repressor REST prevents progenitors from undergoing differentiation. Notably...

Conformational preferences of natural and C3-modified epothilones in aqueous solution.

J. Med. Chem. 51 , 1469-73, (2008)

The conformational properties of the microtubule-stabilizing agent epothilone A ( 1a) and its 3-deoxy and 3-deoxy-2,3-didehydro derivatives 2 and 3 have been investigated in aqueous solution by a comb...