Sephin1
![mRNA synthesis](/media/diy/images/page/figure1-mrna.png)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
![Tyramine Signal Amplification (TSA)](/media/diy/images/page/figure2-01.png)
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
![screening library](/media/diy/images/page/figure3-01.png)
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
![Cell Counting Kit-8 (CCK-8)](/media/diy/images/page/CCK-8.jpg)
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
![SYBR Safe DNA Gel Stain](/media/diy/images/page/SYBR Safe DNA Gel Stain.png)
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
![Inhibitor Cocktails](/media/diy/images/page/Inhibitor Cocktails.jpg)
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Sephin1是内质网应激诱导的PPP1R15A的选择性抑制剂,靶向治疗与错误折叠蛋白的积累相关的疾病[1]。
PPP1R15A是蛋白磷酸酶1的调节亚基,调节应激诱导的eIF2α (真核翻译起始因子2的α亚基),对eIF2α进行去磷酸化。磷酸化的eIF2α减少蛋白合成,阻止错误折叠蛋白质在内质网中的积累。因此,抑制PPP1R15A可以延长eIF2α的磷酸化,有利于治疗与蛋白质错误折叠相关的疾病[1]。
用5 μM的Sephin1处理细胞6小时特异性地干扰PPP1R15A-PP1c复合体,而对PPP115B-PP1c复合体没有影响。因此,在HeLa细胞中,Sephin1可以延长应激(2.5 μg/ml tunicamycin处理)发生后eIF2α的磷酸化,并延迟翻译恢复。在野生型而非PPP1R15A突变的细胞中,Sephin1可以保护细胞免受毒性内质网应激的作用[1]。
在小鼠中,Sephin1以1-5 mg/kg的剂量在给定的时间口服给药,对小鼠转杆实验,总体重的增加和记忆没有不良影响。在MPZ突变(myelin protein zero的丝氨酸63缺失)小鼠中,Sephin1以1mg/kg的剂量一天两次口服给药,可以阻止分子、细胞形态和运动能力缺陷。在SOD1突变(突变和有错误折叠倾向的超氧化物歧化酶1)小鼠中,Sephin1以5 mg/kg剂量一天一次口服给药,可以阻止运动能力缺陷、运动神经元的损失和分子缺陷[1]。
参考文献:
1: Das I, Krzyzosiak A, Schneider K, Wrabetz L, D'Antonio M, Barry N, Sigurdardottir A, Bertolotti A. Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. Science. 2015 Apr 10; 348(6231):239-42.
- 1. Jack P. Antel, et al. "Regulation of stress granule formation in human oligodendrocytes." Nat Commun. 2024 Feb 19;15(1):1524. PMID: 38374028
- 2. Rongjing Wang, Minghui Wang, et al. "Protocol for PPP1R15A-inhibited mouse model establishment with subcutaneous B16F1 tumor and single-cell analysis." STAR Protoc. 2023 Sep 26;4(4):102616. PMID: 37756156
- 3. Wang R, Zhang Y, et al. "Single cell RNA sequencing reveals the suppressive effect of PPP1R15A inhibitor Sephin1 in antitumor immunity." iScience 2023 Feb 17;26(2). PMID: 36718369
- 4. Dawid Krokowski, Raul Jobava, et al. "Stress-induced perturbations in intracellular amino acids reprogram mRNA translation in osmoadaptation independently of the ISR." Cell Rep. 2022 Jul 19;40(3):111092. PMID: 35858571
- 5. Florian Pernin, Julia Xiao Xuan Luo, et al. "Diverse injury responses of human oligodendrocyte to mediators implicated in multiple sclerosis." Brain. 2022 Feb 24;awac075. PMID: 35202462
- 6. Chen Y, Podojil JR, et al. "Sephin1, which prolongs the integrated stress response, is a promising therapeutic for multiple sclerosis." Brain. 2019 Feb 1;142(2):344-361. PMID: 30657878
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 196.64 |
Cas No. | 13098-73-2 |
Formula | C8H9ClN4 |
Solubility | insoluble in H2O; insoluble in EtOH; ≥7.75 mg/mL in DMSO |
Chemical Name | (E)-2-(2-chlorobenzylidene)hydrazinecarboximidamide |
SDF | Download SDF |
Canonical SMILES | ClC1=CC=CC=C1/C=N/NC(N)=N |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验: [1] | |
细胞系 |
HeLa和293T细胞 |
制备方法 |
溶解度有限,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
反应条件 |
6 h |
实验结果 |
Sephin1选择性破坏PPP1R15A-PP1c复合物,但相关的PPP1R15B-PP1c复合物不受影响。Sephin1在应激后延长eIF2a磷酸化,延迟翻译恢复并减弱应激基因如促凋亡蛋白CHOP的表达。 |
动物实验: [1] | |
动物模型 |
SOD1小鼠;SOD1G93A突变C57BL/6J小鼠 |
给药剂量 |
5 mg/kg |
实验结果 |
在SOD1突变小鼠中,5 mg/kg剂量的Sephin1每天一次给药,几乎完全阻止了渐进性体重减轻及其运动缺陷,而Sephin1对野生型小鼠的体重增加或运动功能没有不利影响。Sephin1还防止运动神经元损失相关的SOD1突变小鼠的运动缺陷。 |
注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
References: 1. Das I, Krzyzosiak A, Schneider K et al. Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. Science. 2015 Apr 10;348(6231):239-42. |
质量控制和MSDS
- 批次:
化学结构
![Sephin1](http://www.apexbt.com//media/diy/images/struct/A8708.png)
相关生物数据
![Sephin1 Sephin1](http://www.apexbio.cn/media/diy/images/wb/A8708_1.jpg)