Epothilone B Chemical Properties

Melting point:

95-97°C

alpha 

D21 -35° (c = 0.7 in methanol)

Boiling point:

680.2±55.0 °C(Predicted)

Density 

1.136

storage temp. 

Store at -20°C

solubility 

Soluble in DMSO (up to 40 mg/ml) or in Ethanol (up to 35 mg/ml).

form 

White to off-white solid

pka

13.57±0.70(Predicted)

color 

colorless

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month.

InChIKey

QXRSDHAAWVKZLJ-PVYNADRNSA-N

CAS DataBase Reference

152044-54-7

Safety Information

WGK Germany 

3

HS Code 

29419090

Epothilone B Usage And Synthesis

Description

Epothilone B (152044-54-7) induces microtubule polymerization. Causes cell cycle arrest at the G2-M transition (EC50 = 32 nM for HeLa cells). Induces apoptosis. Cell permeable.

Chemical Properties

White Powder

Uses

Epothilone B (Epo B) is a macrolide that causes the formation of bundles of intracellular microtubules in non-mitotic cells, induces the formation of hyperstable tubulin polymers, and arrests cell cycling in mitosis. It induces mitotic arrest at the G2-M transition in Hs578T and HeLa cells (IC50 = 3 and 32 nM, respectively) as well as in multidrug resistant KB3-1 and KBV-1 cells (IC50 = 16 and 92 nM, respectively). Epo B causes cell cycle arrest at nanomolar IC50 values in cell lines from ovarian, breast, lung, colon, prostate, and squamous cancer.

Uses

Epothilones are polyketide natural products that inhibit cancer cells by a mechanism similar to paclitaxel, and also are effective against paclitaxel-resistant tumours. Epothilone B is what is known as a microtubule stabilizer. When a cell divides, the chromosomes that will end up in each cell are separated by thin filaments called microtubules. Normally these microtubules then break down as the cell division progresses. This class of cytotoxic chemo drugs prevents that break down and thus prevents cells from completing division.

Uses

Epothilone B is a microtubule inhibitor isolated from the myxobacteria, Sorangium cellulosum. Like epothilone A, epothilone B acts by stabilising microtubule formation at the taxol binding site, and causes cell cycle arrest at the G2/M transition, leading to cytotoxicity.

Definition

ChEBI: An epithilone that is epithilone D in which the double bond in the macrocyclic ring has been oxidised to the corresponding epoxide (the S,S stereoisomer).

General Description

Epothilones has antimitotic properties. It prevents microtubule depolymerization and competitively blocks paclitaxel binding to microtubules. Epothilone B is used to treat metastatic breast cancer (MBC).

Biological Activity

Microtubule stabilization agent that promotes tubulin polymerization and induces G 2 -M cell cycle arrest (EC 50 = 3 - 92 nM). Potently inhibits a variety of human cancer cell lines (IC 50 values are 0.13 - 0.64 nM), including MDR cells overexpressing the P-glycoprotein efflux pump. Exhibits potent anticancer activity in numerous human tumor xenografts in vivo .

Biochem/physiol Actions

(-)-Epothilone B is a microtubule (MT) stabilizing drug and natural macrolide antitumor from myxobacteria Sorangium cellulosum. EpoB has similar biological properties to EpoA. However, EpoB is 10-fold more potent than EpoA against P-glycoprotein-expressing multidrug resistant (MDR) cells (IC50 = 2 nM for MDR CCRF-CEM/VBL100 cells). (-)-Epothilone B is similar to paclitaxel in binding displacement, and a substitution for paclitaxel in dependent cell growth. EpoB causes cell cycle arrest (IC50 = 3.5 nM).

Side effects

Patupilone is naturally occurring epothilone B. The major dose-limiting adverse reaction to patupilone is diarrhea, rather than neuropathy. Other significant adverse reactions include fatigue and nausea. In phase I/II studies, severe diarrhea was reported in 14–19% of patients. Hematological toxicity appears to be minimal. Grade 3 peripheral neuropathy was the dose-limiting adverse reaction in one phase I study, along with grade 3 diarrhea[3].

References

1) Goodin et al. (2004), Epothilones: mechanism of action and biologic activity; J. Clin. Oncol., 22 2015
2) Bollag et al. (1995), Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action; Cancer Res., 55 2325.
3) Lipp, H. and J. Hartmann. “Chapter 45 - Cytostatic and cytotoxic drugs.”Side Effects of Drugs Annual (2011):935-962.

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