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ISRIB
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
ISRIB图片
CAS NO:548470-11-7
包装与价格:
包装价格(元)
5mg电议
25mg电议

产品介绍
PERK signaling inhibitor
Cas No.548470-11-7
化学名(1Z,1'Z)-N',N''-((1r,4r)-cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetimidic acid)
Canonical SMILESClC1=CC=C(OC/C(O)=N/[C@@]2([H])CC[C@@](/N=C(O)/COC3=CC=C(Cl)C=C3)([H])CC2)C=C1
分子式C22H24Cl2N2O4
分子量451.34
溶解度≥ 15.03mg/mL in DMSO with gentle warming
储存条件Store at -20°C
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

IC50: 5 nM

ISRIB is a potent inhibitor of PERK signaling.

As one of the four eIF2α kinases in mammalian cells, PERK responds to an accumulation of unfolded proteins in the endoplasmic reticulum.

In vitro: Compared with cis-ISRIB, trans-ISRIB proved 100-fold more potent (IC50 = 5 nM vs IC50 = 600 nM), suggesting that ISRIB interacted with its cellular target stereospecifically. In addition, ISRIB could block the production of endogenous ATF4, while had no obvious effect on XBP1 mRNA splicing and XBP1s production. Meanwhile, ISRIB did not affect activation of the ATF6-branch of the UPR, however, ISRIB could block the downstream of PERK and eIF2α phosphorylation [1].

In vivo: In mouse with a single intraperitoneal injection, ISRIB showed a plasma half-life of 8 hr and readily crossed the blood-brain barrier with quick equilibrium in the central nervous system. The detected brain ISRIB concentrations were found to be several fold higher than its IC50. Moreover, ISRIB-treated mice displayed significant enhancement in spatial and fear-associated learning. Therefore, memory consolidation was inherently limited by the ISR, and ISRIB could release suchbrake. These results showed that ISRIB might contribute to the understanding and treatment of cognitive disorders [1].

Clinical trial: Up to now, ISRIB is still in the preclinical development stage.

Reference:
[1] Sidrauski C, et al.  Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife. 2013 May 28;2:e00498.