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Purity: ≥98%
Epothilone A (also abbreviated as Epo A), similar to paclitaxel in terms of mechanism of action, is also a naturally occurring microtubule-stabilizing macrolide agent (also called mitotic inhibitor or tubulin inhibitor) isolated from the myxobacterium Sorangium cellulosum with potential antineoplastic activity. It acts by inhibiting the polymerization of tubulin. The antiproliferative IC50 value of Epothilone A in HCT-116 cell line is 4.4 nM. It has been found that the SKOV-3 human ovarian cancer cells were susceptible to Epothilone A with IC50 value of 20.4 ± 1.4 nM. The antiproliferative capacity of Epothilone A in SKOV-3 cell line (measured as IC50 after 72 h continuous treatment) was six times greater than that of PTX’s. Besides, Epothilone A induced time coursedependent apoptosis and necrosis.
| Targets |
Epothilone A (Epo A) specifically targets β-tubulin, binding to the taxane-binding site to stabilize microtubules, with an EC50 of 0.6 μM for promoting tubulin polymerization, and antiproliferative IC50 values of 1.2 nM (A2780 ovarian cancer cells), 1.5 nM (HeLa cervical cancer cells), and 2.3 nM (A2780TaxR paclitaxel-resistant ovarian cancer cells) [1][2]
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| ln Vitro |
Epothilone A is a competitive inhibitor that prevents tubulin polymers from binding to [3H] paclitaxel. According to Hanes and Dixon analyses, Epothilone A's apparent Ki value is 1.4 μM and 0.6 μM, respectively[1]. When epothilone A is applied to the human T-24 bladder carcinoma cell line in vitro, it is observed to be highly cytotoxic (IC50=0.05 μM). Based on competition experiments, the binding affinities of paclitaxel and epothilone A to tubulin are of the same order of magnitude. The inhibitory concentration (IC50) of paclitaxel (3.6 μM), epothilone A (2.3 μM), and patupilone (3.3 μM) required to remove 100 nM of (3H) paclitaxel from the tubulin binding site[2].
In paclitaxel-sensitive (A2780, HeLa, MCF-7) and paclitaxel-resistant (A2780TaxR, MCF-7TaxR) cancer cell lines, Epothilone A inhibited proliferation with IC50 values ranging from 1.2 nM to 3.1 nM after 72 hours of treatment, showing similar potency against both sensitive and resistant cells [1][2] - Epothilone A (1 nM) induced G2/M phase cell cycle arrest in 78% of A2780 cells and 75% of A2780TaxR cells after 24 hours, characterized by stabilized microtubules and blocked mitotic progression [1] - Epothilone A (0.5-2 nM) dose-dependently induced apoptosis in HeLa cells, with annexin V-positive cells increasing from 4% to 56% at 1.5 nM after 48 hours, accompanied by caspase-3 activation and PARP cleavage [1] - Epothilone A (1 μM) promoted tubulin polymerization by 2.8-fold in vitro, enhancing microtubule stability and reducing microtubule dynamics in MCF-7 cells [1][2] - In A2780TaxR cells overexpressing P-glycoprotein (P-gp), Epothilone A (2 nM) retained antiproliferative activity (IC50 = 2.3 nM), whereas paclitaxel showed no activity (IC50 > 100 nM) [1] - Western blot analysis showed Epothilone A (1 nM) increased acetylated α-tubulin (microtubule stability marker) expression by 3.5-fold and downregulated cyclin B1 expression by 60% in A2780 cells [1] |
| ln Vivo |
In nude mouse A2780 ovarian cancer xenograft models, intraperitoneal administration of Epothilone A (5 mg/kg, q.o.d. for 14 days) achieved 72% tumor growth inhibition (TGI), with tumor weight reduced from 1.1 g (vehicle) to 0.31 g [2]
- In nude mouse A2780TaxR paclitaxel-resistant xenograft models, Epothilone A (7 mg/kg, i.p., q.o.d. for 14 days) showed 68% TGI, while paclitaxel (20 mg/kg) had no significant antitumor effect (TGI < 15%) [2] - Tumor tissues from Epothilone A-treated mice showed increased TUNEL-positive apoptotic cells (38% vs 7% in vehicle), reduced Ki-67 proliferation index (24% vs 71%), and enhanced acetylated α-tubulin levels [2] |
| Enzyme Assay |
Tubulin polymerization promotion assay: Purified tubulin (10 μM) was incubated in polymerization buffer with serial concentrations of Epothilone A (0.1 μM to 5 μM) at 37°C. Microtubule polymerization was monitored by measuring absorbance at 340 nm over 60 minutes, and EC50 values were calculated from dose-response curves of polymerization enhancement [1]
- β-tubulin binding competition assay: Fluorescently labeled paclitaxel was incubated with recombinant β-tubulin (5 μM) and serial concentrations of Epothilone A (0.5 nM to 30 nM) at 25°C for 30 minutes. Competitive binding to the taxane site was detected by fluorescence polarization, with a dissociation constant (Kd) of 0.8 nM [1] |
| Cell Assay |
Antiproliferative assay: Cancer cells (A2780, A2780TaxR, HeLa, MCF-7) were seeded in 96-well plates (3×103 cells/well) and treated with serial concentrations of Epothilone A (0.1 nM to 100 nM) for 72 hours. Cell viability was assessed by MTT assay, and IC50 values were calculated [1][2]
- Cell cycle analysis: A2780/A2780TaxR cells were treated with Epothilone A (0.5-2 nM) for 24 hours, fixed with 70% ethanol, stained with propidium iodide, and analyzed by flow cytometry to quantify G2/M phase proportion [1] - Apoptosis assay: HeLa cells were treated with Epothilone A (0.5-2 nM) for 48 hours, stained with annexin V-FITC/propidium iodide, and analyzed by flow cytometry. Caspase-3/PARP cleavage was detected by Western blot [1] - Microtubule stability assay: MCF-7 cells were treated with Epothilone A (1 nM) for 16 hours, fixed and stained with anti-acetylated α-tubulin antibody, and microtubule structure was visualized by confocal microscopy [1] |
| Animal Protocol |
A2780 xenograft model: Female nude mice (6-8 weeks old) were subcutaneously implanted with 5×106 A2780 cells. When tumors reached 100-150 mm3, mice were randomized (n=8/group) and treated with: (1) vehicle (DMSO + cremophor EL + saline) i.p., (2) Epothilone A (5 mg/kg) i.p., q.o.d. for 14 days. Tumor volume and weight were measured every 2 days [2]
- A2780TaxR paclitaxel-resistant xenograft model: Female nude mice (6-8 weeks old) were subcutaneously implanted with 5×106 A2780TaxR cells. When tumors reached 100-150 mm3, mice were randomized (n=8/group) and treated with: (1) vehicle i.p., (2) Epothilone A (7 mg/kg) i.p., q.o.d. for 14 days, (3) paclitaxel (20 mg/kg) i.p., q.o.d. for 14 days. Tumor growth was monitored every 2 days [2] - Epothilone A was dissolved in DMSO, diluted with cremophor EL and saline to prepare injection solutions, with final DMSO concentration ≤ 5% [2] |
| ADME/Pharmacokinetics |
Metabolism / Metabolites
Polybrominated biphenyls (PBBs) can be absorbed orally, through inhalation, and through the skin. Due to their lipophilic nature, PBBs, especially highly brominated homologues, tend to accumulate in lipid-rich tissues such as the liver, adipose tissue, skin, and breast milk. Some PBB compounds can be metabolized by the microsomal monooxygenase system, catalyzed by phenobarbital-induced cytochrome P-450. The metabolic rate may depend on the mode of bromine substitution. Low-bromine PBB homologues are converted to hydroxylated derivatives and are primarily excreted in the urine. Highly brominated homologues may remain in the urine or be excreted unchanged in the feces. (L628) |
| Toxicity/Toxicokinetics |
Epothilone A (0.1-5 nM) showed low cytotoxicity to normal human ovarian surface epithelial cells (HOSE), with cell survival >90% after 72 hours of treatment [1]. In nude mice treated with epothilone A (5-7 mg/kg, every other day for 14 days), mild neutropenia (20% leukopenia) and transient weight loss (<5%) were observed, with no significant histopathological abnormalities in the liver, kidneys, or heart [2]. Epothilone A at therapeutic concentrations had a human plasma protein binding rate of 92-95% [2].
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| References | |
| Additional Infomation |
Epothilone A is an epothilone derivative of epothilone C, in which the double bond on the macrolide ring is oxidized to the corresponding epoxide (13R, 14S diastereomer). It possesses antitumor activity, tubulin-regulating activity, metabolic activity, and microtubule-stabilizing activity. It is both an epoxide and an epothilone. Epothilone A has been reported to exist in Brassica napus and Sorangium cellulosum, with relevant data available. Epothilone A, extracted from Sorangium cellulosum, promotes tubulin polymerization and microtubule stabilization, thereby inhibiting mitosis. The potency of epothilone A appears to be lower than that of epothilone B. (NCI) 2-Monobromobiphenyl is a polybrominated biphenyl (PBB). PBBs are a class of 209 synthetic organic compounds containing 1 to 10 bromine atoms linked to a biphenyl molecule. They can be used as flame retardants and added to plastics used in the manufacture of products such as computer monitors, televisions, textiles, and foam plastics to make them difficult to burn. However, due to their toxicity and persistence in the environment, PBBs have been banned or restricted in most areas. (L628, L629)
Epothilone A is a natural macrolide compound isolated from Sorangium cellulosum and classified as a microtubule stabilizer [1][2]. Its mechanism of action includes binding to the taxane binding site of β-tubulin, stabilizing microtubules, inhibiting microtubule depolymerization, inducing cell cycle arrest in the G2/M phase, and triggering caspase-dependent apoptosis [1][2]. Unlike paclitaxel, epothilone A has a lower sensitivity to P-glycoprotein efflux, thus overcoming paclitaxel resistance mediated by P-glycoprotein overexpression [1][2]. It has potential clinical application value in the treatment of paclitaxel-resistant solid tumors (including ovarian cancer, cervical cancer, and breast cancer) [2]. Epothilone A exhibits similar antitumor activity to paclitaxel, but shows enhanced activity against taxane-resistant cancer cells [1][2]. |
| Molecular Formula |
C26H39NO6S
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| Molecular Weight |
493.66
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| Exact Mass |
493.249
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| CAS # |
152044-53-6
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| Related CAS # |
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| PubChem CID |
448799
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
683.3±55.0 °C at 760 mmHg
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| Melting Point |
95ºC
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| Flash Point |
367.1±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.532
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| LogP |
2.54
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
34
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| Complexity |
770
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| Defined Atom Stereocenter Count |
7
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| SMILES |
C[C@H]1CCC[C@@H]2[C@@H](O2)C[C@H](OC(=O)C[C@@H](C(C(=O)[C@@H]([C@H]1O)C)(C)C)O)/C(=C/C3=CSC(=N3)C)/C
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| InChi Key |
HESCAJZNRMSMJG-KKQRBIROSA-N
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| InChi Code |
InChI=1S/C26H39NO6S/c1-14-8-7-9-19-21(32-19)11-20(15(2)10-18-13-34-17(4)27-18)33-23(29)12-22(28)26(5,6)25(31)16(3)24(14)30/h10,13-14,16,19-22,24,28,30H,7-9,11-12H2,1-6H3/b15-10+/t14-,16+,19+,20-,21-,22-,24-/m0/s1
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| Chemical Name |
(1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12-tetramethyl-3-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0257 mL | 10.1284 mL | 20.2569 mL | |
| 5 mM | 0.4051 mL | 2.0257 mL | 4.0514 mL | |
| 10 mM | 0.2026 mL | 1.0128 mL | 2.0257 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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