Epothilone A (Epo A)   中文名称: 埃坡霉素A

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]

Epothilone A 是一种竞争性抑制剂，可防止微管蛋白聚合物与 [3H] 紫杉醇结合。根据Hanes和Dixon分析，埃博霉素A的表观Ki值分别为1.4 μM和0.6 μM[1]。当埃坡霉素 A 在体外应用于人 T-24 膀胱癌细胞系时，观察到它具有高度细胞毒性（IC50=0.05 μM）。根据竞争实验，紫杉醇和埃坡霉素A与微管蛋白的结合亲和力处于同一数量级。从微管蛋白结合位点去除 100 nM (3H) 紫杉醇所需的紫杉醇 (3.6 μM)、埃坡霉素 A (2.3 μM) 和帕图匹隆 (3.3 μM) 的抑制浓度 (IC50)[2]。

---

在紫杉醇敏感（A2780、HeLa、MCF-7）和紫杉醇耐药（A2780TaxR、MCF-7TaxR）癌细胞系中，Epothilone A 抑制细胞增殖，72 小时处理后的 IC50 值范围为 1.2 nM 至 3.1 nM，对敏感和耐药细胞均表现出相似的 potency [1][2]
- 1 nM Epothilone A 处理 24 小时后，78% 的 A2780 细胞和 75% 的 A2780TaxR 细胞发生 G2/M 期细胞周期阻滞，表现为微管稳定和有丝分裂进程受阻 [1]
- Epothilone A（0.5-2 nM）剂量依赖性诱导 HeLa 细胞凋亡，1.5 nM 浓度处理 48 小时后，膜联蛋白 V 阳性细胞比例从 4% 升至 56%，伴随半胱天冬酶 -3 激活和 PARP 切割 [1]
- 1 μM Epothilone A 在体外促进微管蛋白聚合 2.8 倍，增强 MCF-7 细胞中微管稳定性并降低微管动力学 [1][2]
- 在过表达 P- 糖蛋白（P-gp）的 A2780TaxR 细胞中，Epothilone A（2 nM）仍保持抗增殖活性（IC50 = 2.3 nM），而紫杉醇无活性（IC50 > 100 nM）[1]
- Western blot 分析显示，1 nM Epothilone A 使 A2780 细胞中乙酰化 α- 微管蛋白（微管稳定性标志物）表达上调 3.5 倍，细胞周期蛋白 B1 表达下调 60% [1]

在裸鼠 A2780 卵巢癌异种移植模型中，腹腔注射 Epothilone A（5 mg/kg，隔日一次，连续 14 天）的肿瘤生长抑制率（TGI）达 72%，肿瘤重量从溶媒组的 1.1 g 降至 0.31 g [2]
- 在裸鼠 A2780TaxR 紫杉醇耐药异种移植模型中，Epothilone A（7 mg/kg，腹腔给药，隔日一次，连续 14 天）的 TGI 为 68%，而紫杉醇（20 mg/kg）无显著抗肿瘤效果（TGI < 15%）[2]
- Epothilone A 处理组小鼠的肿瘤组织中，TUNEL 阳性凋亡细胞比例达 38%（溶媒组为 7%），Ki-67 增殖指数降至 24%（溶媒组为 71%），乙酰化 α- 微管蛋白水平升高 [2]

微管聚合促进实验：纯化微管蛋白（10 μM）与系列浓度的 Epothilone A（0.1 μM 至 5 μM）在聚合缓冲液中 37°C 孵育。60 分钟内通过检测 340 nm 吸光度监测微管聚合，从聚合增强的剂量 - 反应曲线计算 EC50 值 [1]
- β- 微管蛋白结合竞争实验：荧光标记的紫杉醇与重组 β- 微管蛋白（5 μM）及系列浓度的 Epothilone A（0.5 nM 至 30 nM）25°C 孵育 30 分钟。荧光偏振法检测对紫杉烷结合位点的竞争性结合，Epothilone A 的解离常数（Kd）为 0.8 nM [1]

抗增殖实验：癌细胞（A2780、A2780TaxR、HeLa、MCF-7）接种于 96 孔板（3×103 个细胞 / 孔），用系列浓度的 Epothilone A（0.1 nM 至 100 nM）处理 72 小时。MTT 法评估细胞活力，计算 IC50 值 [1][2]
- 细胞周期分析：A2780/A2780TaxR 细胞用 Epothilone A（0.5-2 nM）处理 24 小时，70% 乙醇固定，碘化丙啶染色，流式细胞术定量 G2/M 期比例 [1]
- 凋亡实验：HeLa 细胞用 Epothilone A（0.5-2 nM）处理 48 小时后，用膜联蛋白 V-FITC/碘化丙啶染色，流式细胞术分析。Western blot 检测半胱天冬酶 -3/PARP 切割 [1]
- 微管稳定性实验：MCF-7 细胞用 Epothilone A（1 nM）处理 16 小时，固定后用抗乙酰化 α- 微管蛋白抗体染色，共聚焦显微镜观察微管结构 [1]

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]

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)

Epothilone A (0.1-5 nM) showed low cytotoxicity in normal human ovarian surface epithelial cells (HOSE), with cell viability > 90% after 72 hours of treatment [1]
- In nude mice treated with Epothilone A (5-7 mg/kg i.p. q.o.d. for 14 days), mild neutropenia (20% reduction in white blood cells) and transient weight loss (<5%) were observed, with no significant histopathological abnormalities in liver, kidney, or heart [2]
- Human plasma protein binding of Epothilone A is 92-95% at therapeutic concentrations [2]

[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.

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)

---

Epothilone A is a natural macrolide compound isolated from the bacterium Sorangium cellulosum, classified as a microtubule-stabilizing agent [1][2]
Its mechanism of action involves binding to the taxane-binding site of β-tubulin, stabilizing microtubules, inhibiting microtubule depolymerization, inducing G2/M cell cycle arrest, and triggering caspase-dependent apoptosis [1][2]
Unlike paclitaxel, Epothilone A overcomes paclitaxel resistance mediated by P-glycoprotein overexpression, due to its lower susceptibility to efflux by P-gp [1][2]
It has potential clinical applications for the treatment of paclitaxel-resistant solid tumors, including ovarian, cervical, and breast cancer [2]
Epothilone A exhibits similar antitumor efficacy to paclitaxel but with improved activity against taxane-resistant cancer cells [1][2]

C26H39NO6S

493.66

493.249

152044-53-6

448799

White to off-white solid powder

1.1±0.1 g/cm3

683.3±55.0 °C at 760 mmHg

95ºC

367.1±31.5 °C

0.0±2.2 mmHg at 25°C

1.532

2.54

137.49

2

8

2

34

770

7

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

HESCAJZNRMSMJG-KKQRBIROSA-N

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

(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

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.08 mg/mL (4.21 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

配方 2 中的溶解度: ≥ 2.08 mg/mL (4.21 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

View More

配方 3 中的溶解度: ≥ 2.08 mg/mL (4.21 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。