| Identification | Back Directory | [Name]
Oxacyclohexadec-13-ene-2,6-dione, 4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl-, (4S,7R,8S,9S,13Z,16S)- | [CAS]
189453-10-9 | [Synonyms]
Epo D
KOS 862
NSC 703147
Epothilone D
Desoxyepothilone B
12,13-Desoxyepothilone B
(3S,7S,14S,15S,16R)-3,15-Dihydroxy-2,2,10,14,16-pentamethyl-7-[1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-6-oxacyclohexadec-9-ene-1,5-dione
(4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-5,5,7,9,13-pentaMethyl-16-[(1E)-1-Methyl-2-(2-Methyl-4-thiazolyl)ethenyl]oxacyclohexadec-13-ene-2,6-dione
Oxacyclohexadec-13-ene-2,6-dione, 4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl-, (4S,7R,8S,9S,13Z,16S)-
Oxacyclohexadec-13-ene-2,6-dione, 4,8-dihydroxy-5,5,7,9,13-pentamethyl -16-(1-methyl-2-(2-methyl-4-thiazolyl)ethenyl)-, (4S-(4R*,7S,8R*,9R*,1 3Z,16R*(E)))- | [Molecular Formula]
C27H41NO5S | [MDL Number]
MFCD27976357 | [MOL File]
189453-10-9.mol | [Molecular Weight]
491.68 |
| Chemical Properties | Back Directory | [Appearance]
White Foam | [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 | [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| |
| Hazard Information | Back Directory | [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. | [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that is epithilone C in which the hydrogen at position 13 of the oxacyclohexadec-13-ene-2,6-dione macrocycle has been replaced by a methyl group. | [Description]
Epothilones are microtubule-stabilizing agents with potential anti-neoplastic actions.1,2,3 They are natural macrolides that have high potency in both taxane-sensitive and taxane-resistant models.2,3 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.3,4 Epothilone D is brain penetrant and reduces neurodegeneration in aged tau transgenic mice.5,6 Effects include improved axonal transport, decreased tau neuropathology, and reduced hippocampal neuron loss.5,6 Epothilone D also rescues microtubule defects and attenuates nigrostriatal degeneration in a mouse model of Parkinson’s disease.4 | [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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