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.

Physicochemical Properties

Molecular Formula	C26H39NO6S
Molecular Weight	493.66
Exact Mass	493.249
CAS #	152044-53-6
Related CAS #	152044-53-6
PubChem CID	448799
Appearance	White to off-white solid powder
Density	1.1±0.1 g/cm3
Boiling Point	683.3±55.0 °C at 760 mmHg
Melting Point	95ºC
Flash Point	367.1±31.5 °C
Vapour Pressure	0.0±2.2 mmHg at 25°C
Index of Refraction	1.532
LogP	2.54
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	2
Heavy Atom Count	34
Complexity	770
Defined Atom Stereocenter Count	7
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
InChi Key	HESCAJZNRMSMJG-KKQRBIROSA-N
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
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
Synonyms	Epothilone-A; EpoA;(1R,5S,6S,7R,10S,14S,16S)-6,10-Dihydroxy-5,7,9,9-tetramethyl-14-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-13,17-dioxabicyclo[14.1.0]heptadecane-8,12-dione
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

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].
ln Vivo
Animal Protocol
ADME/Pharmacokinetics	Metabolism / Metabolites PBBs can be absorbed via oral, inhalation, and dermal routes. Due to their lipophilic nature, PBBs, especially the highly brominated congeners, tend to accumulate in lipid-rich tissues such as the liver, adipose, skin, and breast milk. Certain PBB compounds are metabolized by the microsomal monooxygenase system catalyzed by cytochrome P-450 of the type induced by phenobarbital. The rate of metabolism may depends on the bromine substitution pattern. PBB congeners of low bromine content are transformed into hydroxylated derivatives that are predominately eliminated in the urine. Highly brominated congeners are either retained or excreted unchanged in the feces. (L628)
References	[1]. Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol(R)). J Biol Chem. 1997 Jan 24;272(4):2534-41. [2]. Novel microtubule-targeting agents - the epothilones. Biologics. 2008 Dec;2(4):789-811.
Additional Infomation	Epothilone A is an epithilone that is epothilone C in which the double bond in the macrocyclic lactone ring has been oxidised to the corresponding epoxide (the 13R,14S diastereoisomer). It has a role as an antineoplastic agent, a tubulin modulator, a metabolite and a microtubule-stabilising agent. It is an epoxide and an epothilone. Epothilone A has been reported in Brassica napus and Sorangium cellulosum with data available. Epothilone A is an extract from the myxobacteria Sorangium cellulosum that promotes tubulin polymerization and microtubule stabilization, thereby inhibiting mitosis. Epothilone A appears to be less potent than Epothilone B. (NCI) 2-Monobromobiphenyl is a polybrominated biphenyl. Polybrominated biphenyls (PBBs) are a group of 209 synthetic organic compounds with 1-10 bromine atoms attached to biphenyl. They can be used as flame retardants and may be added to the plastics used to make products like computer monitors, televisions, textiles, and plastic foams to make them difficult to burn. However, the use of PBBs is banned or restricted in most areas due to their toxicity and persistence in the environment. (L628, L629)

Solubility Data

Solubility (In Vitro)

DMSO:99 mg/mL (200.5 mM) Water:<1 mg/mL Ethanol:99 mg/mL (200.5 mM)

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.