WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201280
Description: Epothilone D is a natural polyketide compound isolated from the myxobacterium Sorangium cellulosum. Also known as desoxyepothilone B, epothilone D binds to tubulin and inhibits the disassembly of microtubules, resulting in the inhibition of mitosis, cellular proliferation, and cell motility.
MedKoo Cat#: 201280
Name: Epothilone D
Chemical Formula: C27H41NO5S
Exact Mass: 491.27054
Molecular Weight: 491.68
Elemental Analysis: C, 65.95; H, 8.40; N, 2.85; O, 16.27; S, 6.52
Synonym: (-)-Desoxyepothilone B; (-)-Epothilone D; 12,13-Deoxyepothilone B; 12,13-Desoxyepothilone B; Desoxyepothilone B; Epo D; Epothilone D; KOS 862; KOS862; KOS-862; NSC 703147.
IUPAC/Chemical Name: (4S,7R,8S,9S,16S,Z)-4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-((E)-1-(2-methylthiazol-4-yl)prop-1-en-2-yl)oxacyclohexadec-13-ene-2,6-dione
InChi Key: XOZIUKBZLSUILX-GIQCAXHBSA-N
InChi Code: InChI=1S/C27H41NO5S/c1-16-9-8-10-17(2)25(31)19(4)26(32)27(6,7)23(29)14-24(30)33-22(12-11-16)18(3)13-21-15-34-20(5)28-21/h11,13,15,17,19,22-23,25,29,31H,8-10,12,14H2,1-7H3/b16-11-,18-13+/t17-,19+,22-,23-,25-/m0/s1
SMILES Code: O=C(C[C@@H]1O)O[C@H](/C(C)=C/C2=CSC(C)=N2)C/C=C(C)\CCC[C@H](C)[C@H](O)[C@@H](C)C(C1(C)C)=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 491.68 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
1: Yuan L, Fu Y, Zhang D, Xia YQ, Peng Q, Aubry AF, Arnold ME. Use of a carboxylesterase inhibitor of phenylmethanesulfonyl fluoride to stabilize epothilone D in rat plasma for a validated UHPLC-MS/MS assay. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Oct 15;969:60-8. doi: 10.1016/j.jchromb.2014.08.006. Epub 2014 Aug 12. PubMed PMID: 25151331.
2: Daoust A, Bohic S, Saoudi Y, Debacker C, Gory-FaurÃ© S, Andrieux A, Barbier EL, Deloulme JC. Neuronal transport defects of the MAP6 KO mouse - a model of schizophrenia - and alleviation by Epothilone D treatment, as observed using MEMRI. Neuroimage. 2014 Aug 1;96:133-42. doi: 10.1016/j.neuroimage.2014.03.071. Epub 2014 Apr 3. PubMed PMID: 24704457.
3: Wessjohann LA, Scheid GO, Eichelberger U, Umbreen S. Total synthesis of epothilone D: the nerol/macroaldolization approach. J Org Chem. 2013 Nov 1;78(21):10588-95. doi: 10.1021/jo401355r. Epub 2013 Oct 22. PubMed PMID: 24079664.
4: Sang F, Feng P, Chen J, Ding Y, Duan X, Zhai J, Ma X, Zhang B, Zhang Q, Lin J, Chen Y. Epothilone D and its 9-Methyl analogues: combinatorial syntheses, conformation, and biological activities. Eur J Med Chem. 2013 Oct;68:321-32. doi: 10.1016/j.ejmech.2013.08.003. Epub 2013 Aug 11. PubMed PMID: 23994325.
5: Cartelli D, Casagrande F, Busceti CL, Bucci D, Molinaro G, Traficante A, Passarella D, Giavini E, Pezzoli G, Battaglia G, Cappelletti G. Microtubule alterations occur early in experimental parkinsonism and the microtubule stabilizer epothilone D is neuroprotective. Sci Rep. 2013;3:1837. doi: 10.1038/srep01837. PubMed PMID: 23670541; PubMed Central PMCID: PMC3653217.
6: Fournet V, de LavillÃ©on G, Schweitzer A, Giros B, Andrieux A, Martres MP. Both chronic treatments by epothilone D and fluoxetine increase the short-term memory and differentially alter the mood status of STOP/MAP6 KO mice. J Neurochem. 2012 Dec;123(6):982-96. doi: 10.1111/jnc.12027. Epub 2012 Oct 25. PubMed PMID: 23013328.
7: Zhang B, Carroll J, Trojanowski JQ, Yao Y, Iba M, Potuzak JS, Hogan AM, Xie SX, Ballatore C, Smith AB 3rd, Lee VM, Brunden KR. The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J Neurosci. 2012 Mar 14;32(11):3601-11. doi: 10.1523/JNEUROSCI.4922-11.2012. PubMed PMID: 22423084; PubMed Central PMCID: PMC3321513.
8: 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. Epub 2011 Nov 10. Erratum in: Invest New Drugs. 2012 Dec;30(6):2450. Miranov, Svetlana [corrected to Mironov, Svetlana]. PubMed PMID: 22072399; PubMed Central PMCID: PMC4003559.
9: Monk JP, Villalona-Calero M, Larkin J, Otterson G, Spriggs DS, Hannah AL, Cropp GF, Johnson RG, Hensley ML. A phase 1 study of KOS-862 (Epothilone D) co-administered with carboplatin (ParaplatinÂ®) in patients with advanced solid tumors. Invest New Drugs. 2012 Aug;30(4):1676-83. doi: 10.1007/s10637-011-9731-4. Epub 2011 Aug 9. PubMed PMID: 21826439.
10: Brunden KR, Zhang B, Carroll J, Yao Y, Potuzak JS, Hogan AM, Iba M, James MJ, Xie SX, Ballatore C, Smith AB 3rd, Lee VM, Trojanowski JQ. Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci. 2010 Oct 13;30(41):13861-6. doi: 10.1523/JNEUROSCI.3059-10.2010. PubMed PMID: 20943926; PubMed Central PMCID: PMC2958430.
Information about this agent
The epothilones are a new class of cytotoxic molecules identified as potential chemotherapeutic drugs. As of September 2008[update], epothilones A to F have been identified and characterised. Early studies in cancer cell lines and in human cancer patients indicate superior efficacy to the taxanes. Their mechanism of action is similar, but their chemical structure is simpler. Due to their better water solubility, cremophors (solubilizing agents used for paclitaxel which can affect cardiac function and cause severe hypersensitivity) are not needed. Endotoxin-like properties known from paclitaxel, like activation of macrophages synthesizing inflammatory cytokines and nitric oxide, are not observed for epothilone B. Epothilones were originally identified as metabolites produced by the myxobacterium Sorangium cellulosum. see http://en.wikipedia.org/wiki/Epothilone.
Clinical trials about Epotilones:
Several epothilone analogs are currently undergoing clinical development for treatment of various cancers. One analog, ixabepilone, was approved in October 2007 by the United States Food and Drug Administration for use in the treatment of aggressive metastatic or locally advanced breast cancer no longer responding to currently available chemotherapies. In November 2008, the EMEA has refused a marketing authorisation for Ixabepilone. Epothilone B has proven to contain potent in vivo anticancer activities at tolerate dose levels in several human xenograft models. As a result, epothilone B and its various analogues are currently undergoing various clinical phases (patupilone [EPO906] and sagopilone [SH-Y03757A, ZK-EPO, chemical structure] are in phase II trials; BMS-310705 and BMS-247550 in phase I trials). Results of a phase III trial with ixabepilone in combination with capecitabine in metastatic breast cancer have been announced. see http://en.wikipedia.org/wiki/Epothilone.