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].
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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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分子量 |
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性状 |
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Formula |
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CAS 号 |
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运输条件 |
Room temperature in continental US; may vary elsewhere.
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储存方式 |
Powder |
-20°C |
3 years |
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4°C |
2 years |
In solvent |
-80°C |
6 months |
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-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 |
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请根据半岛bd体育手机客户端 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半岛bd体育手机客户端 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
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1.
请依序添加每种溶剂: 10% DMSO40%PEG3005%Tween-8045% 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。
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2.
请依序添加每种溶剂: 10% DMSO90% (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。
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3.
请依序添加每种溶剂: 10% DMSO90%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。
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以上所有助溶剂都可在本网站选购。
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