Patupilone (Epothilone B)

Mice xenograft model of RPMI 8226 cells

(1S, 3S, 7S, 10R, 11S, 12S, 16R, E)-7, 11-dihydroxy-8, 8, 10, 12, 16-pentamethyl-3-(1-(2-methylthiazol-4-yl)prop-1-en-2-yl)-4, 17-dioxa-bicyclo[14.1.0]heptadecane-5, 9-dione

0–1 uM

2.5 mg/kg–4 mg/kg

1.8 uM (EC0.01) [1], 1.8 uM (EC0.01) [1], 1.8 uM (EC0.01) [1], 1.8 uM (EC0.01) [1], 1.8 uM (EC0.01) [1], 1.8 uM (EC0.01) [1]

In a mouse xenograft model of RPMI 8226 cells, Epothilone B (2.5 mg/kg–4 mg/kg) prolongs survival and suppresses tumor growth. [4] Similarly, in mouse xenograft models of prostate cancer cells, including DU145 and PC3, Epothilone B at the same dose also inhibits tumor growth. [6]

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 B-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 B 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 oained from three different concentrations.

507, 68

Data independently produced by, , , Dr. Helen Sadik, of Johns Hopkins University, Epothilone B (EPO906)purchased from Selleck, Cells were seeded in 96 well paltes, and then treated with the indicated concentration of Epothilone B for 48 h. Cell survival was measured by a standarad MTT assay.

2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO