WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H201280
CAS#: 189453-10-9
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.
Hodoodo Cat#: H201280
Name: Epothilone D
CAS#: 189453-10-9
Chemical Formula: C27H41NO5S
Exact Mass: 491.27
Molecular Weight: 491.680
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
More Info: 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.
| Biological target: | Epothilone D (KOS 862) is a potent microtubule stabilizer. |
| In vitro activity: | At 2DIV, 100 nM EpoD (Epothilone D) treated cultures showed significantly (p < 0.05) reduced cell viability by 32%, vehicle treated control neuron (Fig. 1B). By 3DIV (two days of recurrent treatment), the percentage viability was significantly (p < 0.01 and p < 0.001) reduced by 18% in 10 nM EpoD treated cultures and 37% in 100 nM EpoD treated cultures, compared to vehicle treated controls (Fig. 1C). Cell viability decreased further, to 35% in 10 nM EpoD treated cultures and 56% in 100 nM EpoD, when compared to vehicle treated controls (Fig. 1D), suggesting that higher doses of EpoD are detrimental to neuronal cell growth and survival. Reference: Sci Rep. 2020; 10: 918. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976590/ |
| In vivo activity: | Dendritic spines were analyzed from radially projecting/oblique branches of layer 5 projection neuron apical dendrites at the layer 4/5 boarder (Figures 1A,B). All major morphological spine classes (mushroom, stubby, thin) were represented in all mouse groups (Figure 1C). Initial analysis segregated the total spine population by length – spines (<2.5 μm) and filopodia (>2.5 μm) – and revealed a significant decrease (p < 0.05) in average spine length (Figure 1D), but not filopodial length (Figure 1E), in response to epothilone D treatment relative to vehicle treatment in both brain-injured and sham-operated animals. Furthermore, binning the spines by length showed that epothilone D treatment resulted in a significantly higher proportion (p < 0.05) of shorter (<1.5 μm) spines and significantly lower proportion (p < 0.05) of longer spines (1.5–2.5 μm) (Figure Figure1F1F). With respect to density, spine density was significantly increased (p < 0.05) in sham-operated, but not brain-injured animals (Figure 1G) in response to epothilone D treatment, whereas filopodial density was unaltered in both sham-operated and brain-injured animals (Figure 1H). Analysis of morphological sub-class revealed a significant increase (p < 0.05) specifically in mushroom spines in both brain-injured and sham-operated animals in response to epothilone D treatment (Figure 1I). Reference: Front Cell Neurosci. 2018; 12: 223. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077201/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 100.0 | 203.38 |
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 |
| Formulation protocol: | 1. Xue W, Zhang H, Fan Y, Xiao Z, Zhao Y, Liu W, Xu B, Yin Y, Chen B, Li J, Cui Y, Shi Y, Dai J. Upregulation of Apol8 by Epothilone D facilitates the neuronal relay of transplanted NSCs in spinal cord injury. Stem Cell Res Ther. 2021 May 26;12(1):300. doi: 10.1186/s13287-021-02375-w. PMID: 34039405; PMCID: PMC8157417. 2. Clark JA, Chuckowree JA, Dyer MS, Dickson TC, Blizzard CA. Epothilone D alters normal growth, viability and microtubule dependent intracellular functions of cortical neurons in vitro. Sci Rep. 2020 Jan 22;10(1):918. doi: 10.1038/s41598-020-57718-z. PMID: 31969604; PMCID: PMC6976590. 3. Chuckowree JA, Zhu Z, Brizuela M, Lee KM, Blizzard CA, Dickson TC. The Microtubule-Modulating Drug Epothilone D Alters Dendritic Spine Morphology in a Mouse Model of Mild Traumatic Brain Injury. Front Cell Neurosci. 2018 Jul 30;12:223. doi: 10.3389/fncel.2018.00223. PMID: 30104961; PMCID: PMC6077201. 4. Sandner B, Puttagunta R, Motsch M, Bradke F, Ruschel J, Blesch A, Weidner N. Systemic epothilone D improves hindlimb function after spinal cord contusion injury in rats. Exp Neurol. 2018 Aug;306:250-259. doi: 10.1016/j.expneurol.2018.01.018. Epub 2018 Feb 2. PMID: 29408734. |
| In vitro protocol: | 1. Xue W, Zhang H, Fan Y, Xiao Z, Zhao Y, Liu W, Xu B, Yin Y, Chen B, Li J, Cui Y, Shi Y, Dai J. Upregulation of Apol8 by Epothilone D facilitates the neuronal relay of transplanted NSCs in spinal cord injury. Stem Cell Res Ther. 2021 May 26;12(1):300. doi: 10.1186/s13287-021-02375-w. PMID: 34039405; PMCID: PMC8157417. 2. Clark JA, Chuckowree JA, Dyer MS, Dickson TC, Blizzard CA. Epothilone D alters normal growth, viability and microtubule dependent intracellular functions of cortical neurons in vitro. Sci Rep. 2020 Jan 22;10(1):918. doi: 10.1038/s41598-020-57718-z. PMID: 31969604; PMCID: PMC6976590. |
| In vivo protocol: | 1. Chuckowree JA, Zhu Z, Brizuela M, Lee KM, Blizzard CA, Dickson TC. The Microtubule-Modulating Drug Epothilone D Alters Dendritic Spine Morphology in a Mouse Model of Mild Traumatic Brain Injury. Front Cell Neurosci. 2018 Jul 30;12:223. doi: 10.3389/fncel.2018.00223. PMID: 30104961; PMCID: PMC6077201. 2. Sandner B, Puttagunta R, Motsch M, Bradke F, Ruschel J, Blesch A, Weidner N. Systemic epothilone D improves hindlimb function after spinal cord contusion injury in rats. Exp Neurol. 2018 Aug;306:250-259. doi: 10.1016/j.expneurol.2018.01.018. Epub 2018 Feb 2. PMID: 29408734. |
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-Fauré 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 Lavilléon 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 (Paraplatin®) 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.
