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152044-54-7 molecular structure
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(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 and InChIs

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

Cite this record

CBID:72638 http://www.chembase.cn/molecule-72638.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
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)
CAS Number
152044-54-7
MDL Number
MFCD02101921
PubChem SID
162037563
24724475
PubChem CID
448013

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID
PubChem 448013 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Acid pKa 14.086929  H Acceptors
H Donor LogD (pH = 5.5) 4.122024 
LogD (pH = 7.4) 4.1227245  Log P 4.1227336 
Molar Refractivity 134.76 cm3 Polarizability 53.40498 Å3
Polar Surface Area 109.25 Å2 Rotatable Bonds
Lipinski's Rule of Five false 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
DMSO expand Show data source
Apperance
colorless film expand Show data source
Storage Condition
-20°C expand Show data source
desiccated expand Show data source
protect from light expand Show data source
MSDS Link
Download expand Show data source
German water hazard class
3 expand Show data source
Storage Temperature
-20°C expand Show data source
Target
Microtubule Formation expand Show data source
Purity
≥98% (HPLC) expand Show data source
Salt Data
Free Base expand Show data source
Biological Source
from Sorangium cellulosum expand Show data source
Empirical Formula (Hill Notation)
C27H41NO6S expand Show data source

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich
Selleck Chemicals - S1364 external link
Research Area
Description Cancer
Biological Activity
Description Epothilone B is a Taxol-like microtubule-stabilizing agent with EC0.01 of 1.8 μM.
Targets Tubulin
IC50 1.8 μM (EC0.01) [
In Vitro Epothilone B shows better activity than Epothilone A. The EC0.01 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.
Features
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 (EC0.01), defined as the interpolated concentration capable of inducing an initial slope of 0.01 OD/min rate, is calculated using the formula EC0.01 = concentration/slope and expressed as the mean with standard deviation obtained from three different concentrations.
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.
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
[1] Regueiro-Ren A , et al. Org Lett, 2001, 3(17), 2693-2696.
[2] Bollag DM, et al. Cancer Res, 1995, 55(11), 2325-2333.
[3] Kamath K, et al. Cancer Res, 2003, 63(18), 6026-6031.
[4] Lin B, et al. Blood, 2005, 105(1), 350-357.
[5] Shahabi S, et al. Gynecol Oncol, 2010, 119(2), 345-350.
[6] O'Reilly T, et al. Prostate, 2005, 65(3), 231-240.
[7] Swindell CS, et al. J Med Chem, 1991, 34(3), 1176-1184.
Sigma Aldrich - E2656 external link
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).

PATENTS

PATENTS

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