ISRIB
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
IC50为5 nM。
ISRIB是PERK信号传导的强效抑制剂。
作为哺乳动物细胞中的四种eIF2α激酶之一,PERK应答内质网中未折叠蛋白的积累。
体外:已证实反式ISRIB比顺式ISRIB强效100倍(IC50 = 5 nM对比IC50 = 600 nM),表明ISRIB与其细胞靶点立体特异性相互作用。此外,ISRIB可以阻断内源性ATF4的产生,而对XBP1 mRNA剪接和XBP1的产生没有明显影响。同时,ISRIB不影响UPR的ATF6分支的活化,然而,ISRIB可阻断PERK下游和eIF2α磷酸化[1]。
体内:在单次腹膜内注射的小鼠中,ISRIB表现出8小时的血浆半衰期,并且容易穿过血脑屏障,在中枢神经系统中快速平衡。检测到的脑ISRIB浓度比其IC50高几倍。此外,ISRIB治疗小鼠表现出对空间和恐惧相关学习的显著增强。因此,记忆巩固必定受到ISR的限制,且ISRIB可以解除这种阻碍。这些结果表明,ISRIB可能有助于认知障碍的理解和治疗[1]。
临床试验:到目前为止,ISRIB仍处于临床前研究阶段。
参考文献:
[1] Sidrauski C, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife. 2013 May 28;2:e00498.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 451.34 |
Cas No. | 548470-11-7 |
Formula | C22H24Cl2N2O4 |
Solubility | insoluble in H2O; insoluble in EtOH; ≥15.03 mg/mL in DMSO with gentle warming |
Chemical Name | (1Z,1'Z)-N',N''-((1r,4r)-cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetimidic acid) |
SDF | Download SDF |
Canonical SMILES | ClC1=CC=C(OC/C(O)=N/[C@@]2([H])CC[C@@](/N=C(O)/COC3=CC=C(Cl)C=C3)([H])CC2)C=C1 |
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。 |
Cell experiment:[1] | |
Cell lines |
HEK293T cells |
Reaction Conditions |
200 nM ISRIB for 24 h incubation |
Applications |
Addition of ISRIB alone did not affect cell viability, but caused a strong synergistic effect on ER-stressed cells, reducing colony number and size significantly more than ER-stress alone. This reduction in cell survival resulted from activation of apoptosis as the activity of the executioner caspases 3 and/or 7 was significantly induced under these conditions. Thus, ISRIB could synergize with ER stress to induce apoptosis. |
Animal experiment:[1] | |
Animal models |
Eight to ten-week-old male C57BL/6J mice |
Dosage form |
0.25 mg/kg Injected intraperitoneally |
Applications |
In a Morris water maze, ISRIB-treated mice reached the hidden platform significantly faster compared to vehicle treated controls. The difference was already pronounced by days 3 and 4. |
Note |
The technical data provided above is for reference only. |
References: 1. Sidrauski C, Acosta-Alvear D, Khoutorsky A, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife, 2013, 2: e00498. |
质量控制和MSDS
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