Name: ISRIB (trans-isomer)
Price: 290.00 USD

- Overview
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    Background
    
    ISRIB (trans-isomer) is a potent inhibitor of the integrated stress response (ISR) [1].
    Integrated stress response (ISR) is activated by diverse cellular conditions and rapidly reduces overall protein synthesis while enhancing translation of specific transcripts that support adaptive stress responses. The ISR is mediated by diverse stress-sensing kinases that phosphorylating serine 51 in eukaryotic translation initiation factor alpha (eIF2α) [2].
    ISRIB (trans-isomer) is a potent ISR inhibitor. ISRIB reversed the effects of eIF2α phosphorylation with IC50 value of 5 nM. ISRIB inhibited production of endogenous ATF4 (a cAMP element binding transcription factor). In mouse embryonic fibroblasts (MEFs), ISRIB reversed the increase in the 80S monosomes at the expense of polyribosomes induced by endoplasmic reticulum (ER) stress. In ER-stressed cells, ISRIB reduced cell survival [1]. In stressed cells, ISRIB restored mRNA translation and inhibited stress granule (SG) formation induced by eIF2α phosphorylation [2]. ISRIB inhibited the interaction between eIF2B and eIF2 that located at the core of the ISR [3]. Also, ISRIB was an activator of eIF2B and stabilized activated eIF2B dimers [4].
    In mice, ISRIB significantly increased hippocampus-dependent spatial and fear-associated learning [1].
    
    [1]. Sidrauski C, Acosta-Alvear D, Khoutorsky A, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife, 2013, 2: e00498.
    [2]. Sidrauski C, McGeachy AM, Ingolia NT, et al. The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly. Elife, 2015, 4.
    [3]. Sekine Y, Zyryanova A, Crespillo-Casado A, et al. Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound. Science, 2015, 348(6238): 1027-1030.
    [4]. Sidrauski C, Tsai JC, Kampmann M, et al. Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response. Elife, 2015, 4: e07314.
- Properties
  - Alternative Name
    
    N,N'-((1s,4s)-cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide)
    
    CAS Number
    
    1597403-47-8
    
    Molecular Formula
    
    C22H24Cl2N2O4
    
    Molecular Weight
    
    451.34
    
    Appearance
    
    A solid
    
    Purity
    
    99.99%
    
    Solubility
    
    insoluble in EtOH; insoluble in H2O; insoluble in EtOH; ≥8.96 mg/mL in DMSO with gentle warming
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. Zhang Y, Shi J, et al. "H2A Monoubiquitination Links Glucose Availability to Epigenetic Regulation of the Endoplasmic Reticulum Stress Response and Cancer Cell Death." Cancer Res. 2020;80(11):2243-2256. PMID:32273282
    2. Hongbo Zhang, Clarissa Read, et al. "A cytomegalovirus immunevasin triggers integrated stress 1 response-dependent reorganization of the endoplasmic reticulum." bioRxiv. 2019 May 17.

ISRIB (trans-isomer)

ISRIB (trans-isomer)

Background

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