Epothilone D Chemical Properties

Melting point:

63-66°C

alpha 

D22 -61.3° (c = 2.5 in methanol)

Boiling point:

663.7±55.0 °C(Predicted)

Density 

1.084±0.06 g/cm3(Predicted)

storage temp. 

-20°C Freezer

solubility 

Soluble in DMSO

form 

solid

pka

13.47±0.70(Predicted)

color 

white to off-white

Epothilone D Usage And Synthesis

Description

Epothilones are microtubule-stabilizing agents with potential anti-neoplastic actions. They are natural macrolides that have high potency in both taxane-sensitive and taxane-resistant models. Epothilone D is a desoxy form of epothilone B (Item No. 10924) that inhibits the growth of a variety of cancer cells both in vitro (IC₅₀ values range from 0.97 to 21 nM) and in mice. Epothilone D is brain penetrant and reduces neurodegeneration in aged tau transgenic mice. Effects include improved axonal transport, decreased tau neuropathology, and reduced hippocampal neuron loss. Epothilone D also rescues microtubule defects and attenuates nigrostriatal degeneration in a mouse model of Parkinson’s disease.

Chemical Properties

White Foam

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 D is in phase I clinical testing of in patients with advanced solid tumours. Epothilone D is a cytotoxic macrolide that stabilises malignant cells' microtubules and arrests mitosis, a characteristic it shares with other epothilones. They bind to the same hepatic sites as does paclitaxel (Taxol) in a 1:1 stoichiometric ratio of a, b-tubulin heterodimers.

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 D is in phase I clinical testing of in patients with advanced solid tumours. Epothilone D is a cytotoxic macrolide that stabilises malignant cells'' microtubules and arrests mitosis, a characteristic it shares with other epothilones. They bind to the same hepatic sites as does paclitaxel (Taxol) in a 1:1 stoichiometric ratio of a, b-tubulin heterodimers.

Definition

ChEBI: An epithilone that is epithilone C in which the hydrogen at position 13 of the oxacyclohexadec-13-ene-2,6-dione macrocycle has been replaced by a methyl group.

in vitro

epothilone d is a more potent microtubule stabilizer in vitro than epothilone a or b. in vitro, epothilone d showed potent cytotoxicity in a panel of human tumor cell lines, with similar potency to paclitaxel. it also showed definite advantage over paclitaxel in drug-resistant cell lines, and retained its cytotoxicity against a multidrug resistant cell line over-expressing p-glycoprotein [1].

in vivo

in vivo, antitumor efficacy of epothilone d has been observed in both paclitaxel sensitive and resistant xenografts, as well as certain multidrug resistant xenografts including a doxorubinresistant ccrf-cem leukemic cell xenograft [1].

target

Tubulin

IC 50

2.9 nm for mcf-7 cell line; 2.7 nm for kb-31 cell line; 9.5 nm for ccrf-cem cell line

References

[1] konner j, grisham rn, park j, o'connor oa, cropp g, johnson r, hannah al, hensley ml, sabbatini p, mironov s, danishefsky s, hyman d, spriggs dr, dupont j, aghajanian c. phase i clinical, pharmacokinetic, and pharmacodynamic study of kos-862 (epothilone d) in patients with advanced solid tumors and lymphoma. invest new drugs. 2012 dec;30(6):2294-302. doi: 10.1007/s10637-011-9765-7.

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