ISRIB

SKU: orb1301002

Description

ISRIB (trans-isomer) is a potent PERK inhibitor (IC50=5 nM) that reverses translational suppression and stress granule assembly induced by phosphorylated eIF2α. This small molecule is a valuable research tool for studying the integrated stress response in cellular and animal models of neurodegeneration and other diseases.

Research Area

Neuroscience, Protein Biochemistry

Key Properties

• CAS Number: 1597403-47-8
• MW: 451.34
• Purity: >98%
• Formula: C₂₂H₂₄Cl₂N₂O₄
• SMILES: Clc1ccc(OCC(=O)N[C@H]2CC[C@@H](CC2)NC(=O)COc2ccc(Cl)cc2)cc1
• Target: Ribosome
• Solubility: DMSO (up to 5 mg/ml with warming)

Bioactivity

• Target IC50:
  PERK:5 nM
• In Vivo:
  METHODS: To investigate the effects on memory, ISRIB (0.25-2.5 mg/kg) was administered intraperitoneally to CD-1 mice. RESULTS: ISRIB-treated mice showed significant enhancement in spatial and fear-related learning.
• In Vitro:
  METHODS: HEK293T cells were treated with clindamycin (2 µg/mL) to induce ER stress and with ISRIB (trans-isomer) or ISRIB (cis-isomer) (0-1 µM) for 7 h. The ATF4 fluorokinase reporter gene was detected. RESULTS: ISRIB (trans-isomer) was 100-fold more potent (IC50=5 nM) than ISRIB (cis-isomer) (IC50=600 nM), suggesting that the compound interacts stereospecifically with its cellular target. METHODS: HEK293T cells were treated with Tm (1 µg/mL) and ISRIB (200 nM) for 1 h. Translation and mRNA changes were detected. RESULTS: ISRIB completely blocked the translational changes that occurred under ER stress. A large number of genes with significant changes in expression upon stress collapsed to the center of the graph under ISRIB and Tm co-treatment.
• Cell Research:
  U2OS cells are plated on 96-well plates and left to recover overnight. Cells are treated with either with 2 μg/ml tunicamycin or 100 nM thapsigargin in the presence or absence of 100 nM ISRIB or with ISRIB alone for the indicated and the level of eIF2α phosphorylation is determined.

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

trans-ISRIB

Compound Identifiers

PubChem CID

1011240