Epothilone B Property

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

optical activity

-35.021 (methanol)

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

WGK Germany 

3

HS Code 

29419090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H300Fatal if swallowed

H310Fatal in contact with skin

H315Causes skin irritation

H317May cause an allergic skin reaction

H341Suspected of causing genetic defects

H360May damage fertility or the unborn child

H372Causes damage to organs through prolonged or repeated exposure

H410Very toxic to aquatic life with long lasting effects

Precautionary statements

P201Obtain special instructions before use.

P202Do not handle until all safety precautions have been read and understood.

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P262Do not get in eyes, on skin, or on clothing.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P272Contaminated work clothing should not be allowed out of the workplace.

P273Avoid release to the environment.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P281Use personal protective equipment as required.

P301+P310IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.

P302+P350IF ON SKIN: Gently wash with plenty of soap and water.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P308+P313IF exposed or concerned: Get medical advice/attention.

P310Immediately call a POISON CENTER or doctor/physician.

P314Get medical advice/attention if you feel unwell.

P321Specific treatment (see … on this label).

P322Specific measures (see …on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P333+P313IF SKIN irritation or rash occurs: Get medical advice/attention.

P361Remove/Take off immediately all contaminated clothing.

P362Take off contaminated clothing and wash before reuse.

P363Wash contaminated clothing before reuse.

P391Collect spillage. Hazardous to the aquatic environment

P405Store locked up.

P501Dispose of contents/container to..…

Epothilone B Chemical Properties,Usage,Production

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.