For research use only. Not for therapeutic Use.
ISRIB is a brain-penetrant inhibitor of integrated stress response (ISR). Persistent activation of the ISR has been linked to the development of several neurological disorders as ISR represses translation through inhibiting eIF2B. ISRIB inhibits the ISR by promoting the nucleotide exchange activity of eIF2B and recovering the translation, and thus can be used for neurological disorders research[1][2][3].
ISRIB (200 nM, 2 h) blocks stress granule formation induced by eIF2α phosphorylation in U2OS cells[3].
ISRIB (0.25 mg/kg, i.p., daily) restores translation in prion-diseased mice at downstream of eIF2α phosphorylation, confering neuroprotection in prion-diseased mice [2].
| Catalog Number | I011731 |
| CAS Number | 548470-11-7 |
| Synonyms | 2-(4-chlorophenoxy)-N-[4-[[2-(4-chlorophenoxy)acetyl]amino]cyclohexyl]acetamide |
| Molecular Formula | C22H24Cl2N2O4 |
| Purity | ≥95% |
| InChI | InChI=1S/C22H24Cl2N2O4/c23-15-1-9-19(10-2-15)29-13-21(27)25-17-5-7-18(8-6-17)26-22(28)14-30-20-11-3-16(24)4-12-20/h1-4,9-12,17-18H,5-8,13-14H2,(H,25,27)(H,26,28) |
| InChIKey | HJGMCDHQPXTGAV-UHFFFAOYSA-N |
| SMILES | C1CC(CCC1NC(=O)COC2=CC=C(C=C2)Cl)NC(=O)COC3=CC=C(C=C3)Cl |
| Reference | [1]. Zyryanova AF, et al. ISRIB Blunts the Integrated Stress Response by Allosterically Antagonising the Inhibitory Effect of Phosphorylated eIF2 on eIF2B. Mol Cell. 2021 Jan 7;81(1):88-103.e6. [2]. Halliday M, et al. Partial restoration of protein synthesis rates by the small molecule ISRIB prevents neurodegeneration without pancreatic toxicity. Cell Death Dis. 2015 Mar 5;6(3):e1672. [3]. Sidrauski C, et al. The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly. Elife. 2015 Feb 26;4:e05033. |
