(1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione

• ChemBase ID: 72638
• Molecular Formular: C27H41NO6S
• Molecular Mass: 507.68254
• Monoisotopic Mass: 507.26545904
• SMILES: O1[C@@]2(CCC[C@H]([C@@H]([C@H](C(=O)C([C@H](CC(=O)O[C@@H](C[C@H]12)/C(=C/c1nc(sc1)C)/C)O)(C)C)C)O)C)C
• Canonical SMILES: O=C1O[C@@H](C[C@@H]2O[C@]2(C)CCC[C@H]([C@@H]([C@H](C(=O)C([C@H](C1)O)(C)C)C)O)C)/C(=C/c1csc(n1)C)/C
• InChI: InChI=1S/C27H41NO6S/c1-15-9-8-10-27(7)22(34-27)12-20(16(2)11-19-14-35-18(4)28-19)33-23(30)13-21(29)26(5,6)25(32)17(3)24(15)31/h11,14-15,17,20-22,24,29,31H,8-10,12-13H2,1-7H3/b16-11+/t15-,17+,20-,21-,22-,24-,27+/m0/s1
• InChIKey: QXRSDHAAWVKZLJ-PVYNADRNSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione; (1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[(1E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
• IUPAC Traditional name: (1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione; epothilone B
• Synonyms: (-)-Epothilone B; EPO906; EpoB; Patupilone; Epothilone B(EPO906)

Database IDs

• CAS Number: 152044-54-7
• MDL Number: MFCD02101921
• PubChem SID: 162037563; 24724475
• PubChem CID: 448013

CALCULATED PROPERTIES

• Acid pKa: 14.086929
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): 4.122024
• LogD (pH = 7.4): 4.1227245
• Log P: 4.1227336
• Molar Refractivity: 134.76 cm^3
• Polarizability: 53.40498 Å^3
• Polar Surface Area: 109.25 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: false

PROPERTIES

Physical Property

• Solubility: DMSO
• Apperance: colorless film

Safety Information

• Storage Condition: -20°C; desiccated; protect from light
• German water hazard class: 3
• Storage Temperature: -20°C

Pharmacology Properties

• Target: Microtubule Formation

Product Information

• Purity: ≥98% (HPLC)
• Salt Data: Free Base
• Biological Source: from Sorangium cellulosum
• Empirical Formula (Hill Notation): C27H41NO6S

DETAILS

Selleck Chemicals - S1364

Research Area

• Description: Cancer

Biological Activity

• Description: Epothilone B is a Taxol-like microtubule-stabilizing agent with EC_0.01 of 1.8 μM.
• Targets: Tubulin
• IC50: 1.8 μM (EC_0.01) ^[
• In Vitro: Epothilone B shows better activity than Epothilone A. The EC_0.01 of Epothilone B is 1.8 μM. Epothilone B potently inhibits cell proliferation in HCT116 cells, with IC50 of 0.8 nM. ^[1]Epothilone B induces mitotic arrest and displays cytotoxicity in KB3-1, KBV-1, Hela, and Hs578T cells, with IC50 of 3 nM to 92 nM. Epothilone B competes with Taxol in binding to microtubules, with IC50 of 3.3 μM. ^[2]In MCF-7 cells overexpressing GFP-α-tubulin, Epothilone B (3.5 nM) efficiently blocks microtubule dynamics. Meanwhile, Epothilone B induces mitotic arrest with IC50 of 3.5 nM. ^[3]In multiple myeloma (MM) cells, including RPMI 8226, U266, MM.1S, LR5, and MR20, Epothilone B directly suppresses proliferation with IC50 of 1 nM to 10 nM. Similarly, Epothilone B (10 nM) also induces cell cycle arrest and apoptosis. ^[4]A recent study reveals that, in ovarian cancer Hey cells, Epothilone B (5 nM–100 nM) enhances surface epithelial cell adhesion antigen (EpCAM), without affecting the transcription or the total cellular level of EpCAM. ^[5]
• In Vivo: In a mouse xenograft model of RPMI 8226 cells, Epothilone B (2.5 mg/kg–4 mg/kg) prolongs survival and suppresses tumor growth. ^[4]Similarly, in mouse xenograft models of prostate cancer cells, including DU145 and PC3, Epothilone B at the same dose also inhibits tumor growth. ^[6]
• Clinical Trials: A Phase III clinical trial for Epothilone B in patients with ovarian, primary fallopian, or peritoneal cancer has been completed.

Protocol

• Protocol: Kinase Assay ^[1]
• Tubulin polymerization assay: Calf brain microtubule proteins (MTP) are purified, which includes approximately 15%–20% microtubule associated proteins. The buffer (MES buffer) used for the Epothilone B-microtubule studies contains 0.1 M 2-morpholinoethanesulfonic acid (MES), 1 mM EGTA, 0.5 mM MgCl₂, and 3 M glycerol at pH 6.6. Samples for electron microscopy are placed on carbon-over-Parlodion-coated grids (300 mesh) and negatively stained with 2% uranyl acetate. Microtubule assembly in the presence or absence of Epothilone B is monitored spectrophotometrically by using a spectrophotometer equipped with a thermostatically regulated liquid circulator. The temperature is held at 35 °C and changes in turbidity (representative of polymer mass) are monitored at 350 nm. Effective concentration (EC_0.01), defined as the interpolated concentration capable of inducing an initial slope of 0.01 OD/min rate, is calculated using the formula EC_0.01 = concentration/slope and expressed as the mean with standard deviation obtained from three different concentrations.
• Protocol: Cell Assay ^[2]
• Cell Lines: KB3-1, KBV-1, Hela, and Hs578T cells
• Concentrations: 0–1 μM
• Incubation Time: 72 hours
• Methods: For mitotic block and aberrant mitosis, cells are plated either in 48-well plates (for trypan blue and cell counting) or onto coverslips. After 24 hours, cells are treated with Epothilone B and scored at regular intervals. For the cytotoxicity analysis, cells are counted and scored as trypan blue positive or negative. Concurrently, coverslips andaliquots of cells in the culture supernatant are fixed and stained with Hoechst33342 in PBS. These cells are scored for cells blocked at the G2/M transition and aberrant mitosis.
• Protocol: Animal Study ^[4]
• Animal Models: Mice xenograft model of RPMI 8226 cells
• Formulation: Dissolved in30% PEG-300
• Doses: 2.5 mg/kg–4 mg/kg
• Administration: Inject intravenously

References

• References: [1] Regueiro-Ren A , et al. Org Lett, 2001, 3(17), 2693-2696.
• References: [2] Bollag DM, et al. Cancer Res, 1995, 55(11), 2325-2333.
• References: [3] Kamath K, et al. Cancer Res, 2003, 63(18), 6026-6031.
• References: [4] Lin B, et al. Blood, 2005, 105(1), 350-357.
• References: [5] Shahabi S, et al. Gynecol Oncol, 2010, 119(2), 345-350.
• References: [6] O'Reilly T, et al. Prostate, 2005, 65(3), 231-240.
• References: [7] Swindell CS, et al. J Med Chem, 1991, 34(3), 1176-1184.

Sigma Aldrich - E2656

Biochem/physiol Actions
(-)-Epothilone B is a microtubule (MT) stabilizing drug and natural macrolide antitumor from myxobacteria Sorangium cellulosum. EpoB has similar biological properties to EpoA. However, EpoB is 10-fold more potent than EpoA against P-glycoprotein-expressing multidrug resistant (MDR) cells (IC50 = 2 nM for MDR CCRF-CEM/VBL100 cells). (-)-Epothilone B is similar to paclitaxel in binding displacement, and a substitution for paclitaxel in dependent cell growth. EpoB causes cell cycle arrest (IC50 = 3.5 nM).

REFERENCES

• Regueiro-Ren A , et al. Org Lett, 2001, 3(17), 2693-2696.
• Bollag DM, et al. Cancer Res, 1995, 55(11), 2325-2333.
• Kamath K, et al. Cancer Res, 2003, 63(18), 6026-6031.
• Lin B, et al. Blood, 2005, 105(1), 350-357.
• Shahabi S, et al. Gynecol Oncol, 2010, 119(2), 345-350.
• O'Reilly T, et al. Prostate, 2005, 65(3), 231-240.
• Swindell CS, et al. J Med Chem, 1991, 34(3), 1176-1184.