Epothilone D

Bezeichnung:Epothilone D

CAS-Nr189453-10-9

Englisch Name:Epothilone D

CBNumberCB41214330

SummenformelC27H41NO5S

Molgewicht491.68

MOL-Datei189453-10-9.mol

Epothilone D physikalisch-chemischer Eigenschaften

Schmelzpunkt	63-66°C
alpha	D22 -61.3° (c = 2.5 in methanol)
Siedepunkt	663.7±55.0 °C(Predicted)
Dichte	1.084±0.06 g/cm3(Predicted)
storage temp.	-20°C Freezer
Löslichkeit	Soluble in DMSO
Aggregatzustand	solid
pka	13.47±0.70(Predicted)
Farbe	white to off-white
InChIKey	XOZIUKBZLSUILX-GIQCAXHBSA-N
SMILES	O1[C@H](/C(/C)=C/C2=CSC(C)=N2)CC=C(C)CCC[C@H](C)[C@H](O)[C@@H](C)C(=O)C(C)(C)[C@@H](O)CC1=O \|t:13\|

Epothilone D Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
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.
Chemische Eigenschaften
White Foam
Verwenden
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that is epithilone C in which the hydrogen at position 13 of the oxacyclohexadec-13-ene-2,6-dione macrocycle has been replaced by a methyl group.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
Einzelnachweise
[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.

Epothilone D Upstream-Materialien And Downstream Produkte

Epothilone D Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

189453-10-9, Epothilone D Verwandte Suche:

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