Bafilomycin A1 (BafA1) 是特异性,可逆的V-ATPase抑制剂,IC50值为 4-400 nmol/mg。Bafilomycin A1,大环内酯类抗生素, 是一种自噬 (autophagy) 晚期阶段抑制剂。Bafilomycin A1 阻断自噬体与溶酶体的融合,并抑制培养细胞溶酶体中的酸化和蛋白质降解。Bafilomycin A1 也诱导调亡 (apoptosis)。
生物活性 | Bafilomycin A1 (BafA1) is a specific and reversible inhibitor ofvacuolar H+-ATPase(V-ATPase) withIC50values of 4-400 nmol/mg. Bafilomycin A1, a macrolideantibiotic, is also used as anautophagyinhibitor at the late stage. Bafilomycin A1 blocks autophagosome-lysosome fusion and inhibits acidification and protein degradation in lysosomes of cultured cells. Bafilomycin A1 inducesapoptosis[1][2][3]. |
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体外研究 (In Vitro) | Bafilomycin A1 is treated to different types of membrane ATPases with the I50of 400 nmol/mg, 4 nmol/mg and 50 nmol/mg for the vacuolar ATPases of a fungus (N. crassa), a plant (Z. mays), and an animal (bovine abrenal medulla). The I50values refer as μmol of Bafilomycin A1 per mg of protein giving 50% inhibition of ATPase activity[1]. Bafilomycin A1 ((-)-Bafilomycin A1) disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion[2]. Bafilomycin A1 at a low concentration (1 nM) effectively and specifically inhibits and kills pediatric B-cell acute lymphoblastic leukemia cells. It targets both early and late stages of the autophagy pathway, mitochondria and induces caspase-independent apoptosis. Bafilomycin A1 induces the binding of Beclin 1 to Bcl-2, which further inhibits autophagy and promotes apoptotic cell death[5]. The growth of the BEL-7402 hepatocellular carcinoma and HO-8910 ovarian cancer cell lines are retarded and the metastatic potential is inhibited by Bafilomycin A1. Transmission electron microscopy and assays of capsase-3 and -9 suggest that Bafilomycin A1 induces apoptosis[6]. Bafilomycin A1 inhibits the growth of a variety of cultured cells dose-dependently, including golden hamster embryo and NIH-3T3 fibroblasts, whether or not they are transformed, and PC12 and HeLa cells. The IC50of Bafilomycin A1 for inhibition of cell growth ranges from 10 to 50 nM[7].
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体内研究 (In Vivo) | Chronic treatment with low-dose Bafilomycin A1 (0.1 mg/kg) slightly inhibits the tumor volume, but the final tumor volume does not differ significantly from the control. However, chronic treatment with high dose Bafilomycin A1 (1 mg/kg) inhibits the tumor growth significantly, compared with controls, after 21 days[8]. Bafilomycin A1 (0.1 mg/kg or 1 mg/kg; i.p. daily for 3 days) extends the survival of B-cell acute lymphoblastic leukemia (B-ALL) xenograft mice with advanced disease[9].
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结构分类 | - Antibiotics
- Macrolide Antibiotics
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来源 | Streptomyces griseus strains |
运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 100 mg/mL(160.56 mM;Need ultrasonic) H2O :< 0.1 mg/mL (ultrasonic;warming;heat to 60℃)(insoluble) 配制储备液 1 mM | 1.6056 mL | 8.0279 mL | 16.0557 mL | 5 mM | 0.3211 mL | 1.6056 mL | 3.2111 mL | 10 mM | 0.1606 mL | 0.8028 mL | 1.6056 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用;
以下溶剂前显示的百 分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (4.01 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (4.01 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 2. 请依序添加每种溶剂: 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (3.34 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.34 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (3.34 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.34 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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