Molecular Weight(MW): 493.66
Epothilone A is a paclitaxel-like microtubule-stabilizing agent with EC0.01 of 2 μM.
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|Description||Epothilone A is a paclitaxel-like microtubule-stabilizing agent with EC0.01 of 2 μM.|
Epothilone A, discovered from the myxobacterium Sorangium cellulosum, is a Taxol-like microtubule-stabilizing agent that induces tubulin polymerization, leading to cell cycle arrest at the G2-M transition, cytotoxicity, and apoptosis. Epothilone A potently inhibits cell proliferation in HCT116 cells, with IC50 of 4.4 nM.  Epothilone A also displays cytotoxicity in KB3-1, KBV-1, Hela, and Hs578T cells, with IC50 values ranging from 13 nM to 160 nM. Epothilone A is more water soluble than Taxol and competes with Taxol in binding with microtubules, with IC50 of 2.3 μM.  However, both Epothilone A and Taxol don't share a common pharmacophore and exploits the tubulin-binding pocket uniquely and independently.  Recently, it is found that microbiological transformation of Epothilone A by Aspergillus niger AS 3.739 yields several metabolites that is also toxic to MCF-7 cells, but with much higher IC50 values. 
Tubulin polymerization assay:Calf brain microtubule proteins (MTP) are purified, which includes approximately 15%–20% microtubule associated proteins. The buffer (MES buffer) used for the Epothilone A-microtubule studies contains 0.1 M 2-morpholinoethanesulfonic acid (MES), 1 mM EGTA, 0.5 mM MgCl2, and 3 M glycerol at pH 6.6. Samples for electron microscopy are placed on carbon-over-Parlodion-coated grids (300 mesh) and negatively stained with 2% uranyl acetate. Microtubule assembly in the presence or absence of Epothilone A is monitored spectrophotometrically by using a spectrophotometer equipped with a thermostatically regulated liquid circulator. The temperature is held at 35 °C and changes in turbidity (representative of polymer mass) are monitored at 350 nm. Effective concentration (EC0.01), defined as the interpolated concentration capable of inducing an initial slope of 0.01 OD/min rate, is calculated using the formula EC0.01 = concentration/slope and expressed as the mean with standard deviation obtained from three different concentrations.
-  Regueiro-Ren A , et al. Org Lett, 2001, 3(17), 2693-2696.
-  Bollag DM, et al. Cancer Res, 1995, 55(11), 2325-2333.
-  Nettles JH, et al. Science, 2004, 305(5685), 866-869.
|In vitro||DMSO||99 mg/mL (200.54 mM)|
|Ethanol||99 mg/mL (200.54 mM)|
* 1 mg/ml means slightly soluble or insoluble.
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