Azoramide 是一种口服有效的未折叠蛋白反应 (UPR) 小分子调节剂。Azoramide 改善 ER 蛋白质折叠和提高 ER 伴侣能力，共同保护细胞免受 ER 应激。Azoramide 通过调节未折叠蛋白反应减轻 PLA2G6 突变体诱导的 ER 应激，并增强 CERB 信号以挽救线粒体功能，从而防止 DA 神经元凋亡 (apoptosis)。Azoramide 具有抗糖尿病活性。
| 生物活性 | Azoramide is a potent, orally active small-molecule modulator of the unfolded protein response (UPR). Azoramide improves ER protein folding and elevates ER chaperone capacity, which together protects cells against ER stress. Azoramide alleviates PLA2G6 mutant-induced ER stress through modulating unfolded protein response, and enhances the CERB signaling to rescue mitochondrial function, thereby preventingapoptosisof DA neurons. Azoramide has antidiabetic activity[1][2]. |
体外研究
(In Vitro) | Azoramide (0.01-100 μM; 0-24 h; Huh7 cells) regulates ER folding and secretion capacity without inducing ER stress[1].
Azoramide (15 μM; 2-16 h; Huh7 cells) protects cells from induced ER stress. Azoramide counteractsTunicamycin(Tm, HY-A0098)-induced ATF6LD-Cluc secretion and Tm-induced decrease of ASGR-Cluc secretion. Azoramide suppresses Tm-induced GRP78 and CHOP protein expression[1].
Azoramide (15 μM; 2-16 h; Hepa 1-6 cells) alters ER calcium homeostasis and retains a greater fraction of Ca2+in the ER[1].
Azoramide (0-10 μM; 5 d) attenuates loss of PLA2G6D331Y/D331YiPSC-derived midbrain DA neurons[2].
Azoramide (10 μM; 5 d) reduces the increase in ROS and ameliorates the decline in mitochondrial membrane potential in PLA2G6D331Y/D331Ymidbrain DA neurons[2].
Azoramide (10 μM; 0-30 d) suppresses mitochondrial fragmentation in PLA2G6D331Y/D331Ymidbrain DA neurons[2].
Cell Viability Assay[2] | Cell Line: | DA neurons | | Concentration: | 0, 0.1, 0.3, 1, 3, and 10 μM | | Incubation Time: | 5 days | | Result: | Enhanced cell viability with 27 and 39% for 3 and 10 μM, respectively. |
Western Blot Analysis[2] | Cell Line: | DA neurons | | Concentration: | 10 μM | | Incubation Time: | 24 hours | | Result: | Decreased the cleaved level of caspase 3 and the ratio of Bax/Bcl2 in PLA2G6 mutant neurons.
Enhanced expression of CREB in PLA2G6 mutant neurons. |
Western Blot Analysis[2] | Cell Line: | DA neurons | | Concentration: | 10 μM | | Incubation Time: | 30 days | | Result: | Suppressed increased expression of UPR proteins, elevated the decreased expression level of mfn1, and inhibited the elevated expression levels of DRP1 and Fis1 in PLA2G6 mutant neurons |
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体内研究
(In Vivo) | Azoramide (150 mg/kg; p.o.; daily, for 7 d; Huh7 cells;ob/obmice) improves glucose homeostasis in mice with genetic obesity and preserves beta cell function and survival during metabolic ER stress[1].
| Animal Model: | Maleob/obmice (9-12 weeks of age)[1] | | Dosage: | 150 mg/kg | | Administration: | Oral administration; daily, for 7 days | | Result: | Reduces ER stress and improves metabolism in ob/ob mice.
Increased the levels of Pdx1 mRNA and improved beta cell function. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : ≥ 30 mg/mL(97.14 mM) Ethanol :< 1 mg/mL (ultrasonic)(insoluble) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 3.2380 mL | 16.1901 mL | 32.3803 mL | | 5 mM | 0.6476 mL | 3.2380 mL | 6.4761 mL | | 10 mM | 0.3238 mL | 1.6190 mL | 3.2380 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 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (8.10 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (8.10 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (8.10 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (8.10 mM，饱和度未知) 的澄清溶液。 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。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (8.10 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (8.10 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 25.0 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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