WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 555948
CAS#: 548470-11-7
Description: ISRIB is a potent PERK inhibitor. ISRIB antagonizes the activation of the integrated stress response (ISR) by phosphorylated translation initiation factor 2, eIF2(αP). ISRIB and eIF2(αP) bind distinct sites in their common target, eIF2B, a guanine nucleotide exchange factor for eIF2.
MedKoo Cat#: 555948
Name: ISRIB
CAS#: 548470-11-7
Chemical Formula: C22H24Cl2N2O4
Exact Mass: 450.1113
Molecular Weight: 451.344
Elemental Analysis: C, 58.55; H, 5.36; Cl, 15.71; N, 6.21; O, 14.18
Related CAS #: 1597403-47-8 (trans-isomer) 548470-11-7
Synonym: ISRIB;
IUPAC/Chemical Name: 2-(4-Chlorophenoxy)-N-[4-[[2-(4-chlorophenoxy)acetyl]amino]cyclohexyl]acetamide
InChi Key: HJGMCDHQPXTGAV-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(NC1CCC(NC(COC2=CC=C(Cl)C=C2)=O)CC1)COC3=CC=C(Cl)C=C3
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: To be determined
Shelf Life: >2 years if stored properly
Drug Formulation: To be determined
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 15.0 |
The following data is based on the product molecular weight 451.344 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
1: Zyryanova AF, Kashiwagi K, Rato C, Harding HP, Crespillo-Casado A, Perera LA, Sakamoto A, Nishimoto M, Yonemochi M, Shirouzu M, Ito T, Ron D. 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. doi: 10.1016/j.molcel.2020.10.031. Epub 2020 Nov 20. PMID: 33220178; PMCID: PMC7837216.
2: Bugallo R, Marlin E, Baltanás A, Toledo E, Ferrero R, Vinueza-Gavilanes R, Larrea L, Arrasate M, Aragón T. Fine tuning of the unfolded protein response by ISRIB improves neuronal survival in a model of amyotrophic lateral sclerosis. Cell Death Dis. 2020 May 26;11(5):397. doi: 10.1038/s41419-020-2601-2. PMID: 32457286; PMCID: PMC7250913.
3: Young-Baird SK, Lourenço MB, Elder MK, Klann E, Liebau S, Dever TE. Suppression of MEHMO Syndrome Mutation in eIF2 by Small Molecule ISRIB. Mol Cell. 2020 Feb 20;77(4):875-886.e7. doi: 10.1016/j.molcel.2019.11.008. Epub 2019 Dec 10. PMID: 31836389; PMCID: PMC7035991.
4: Anand AA, Walter P. Structural insights into ISRIB, a memory-enhancing inhibitor of the integrated stress response. FEBS J. 2020 Jan;287(2):239-245. doi: 10.1111/febs.15073. Epub 2019 Nov 7. PMID: 31550413.
5: Rabouw HH, Langereis MA, Anand AA, Visser LJ, de Groot RJ, Walter P, van Kuppeveld FJM. Small molecule ISRIB suppresses the integrated stress response within a defined window of activation. Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):2097-2102. doi: 10.1073/pnas.1815767116. Epub 2019 Jan 23. PMID: 30674674; PMCID: PMC6369741.
6: Zyryanova AF, Weis F, Faille A, Alard AA, Crespillo-Casado A, Sekine Y, Harding HP, Allen F, Parts L, Fromont C, Fischer PM, Warren AJ, Ron D. Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B. Science. 2018 Mar 30;359(6383):1533-1536. doi: 10.1126/science.aar5129. PMID: 29599245; PMCID: PMC5889100.
7: Wong YL, LeBon L, Edalji R, Lim HB, Sun C, Sidrauski C. The small molecule ISRIB rescues the stability and activity of Vanishing White Matter Disease eIF2B mutant complexes. Elife. 2018 Feb 28;7:e32733. doi: 10.7554/eLife.32733. PMID: 29489452; PMCID: PMC5829914.
8: Hosoi T, Kakimoto M, Tanaka K, Nomura J, Ozawa K. Unique pharmacological property of ISRIB in inhibition of Aβ-induced neuronal cell death. J Pharmacol Sci. 2016 Aug;131(4):292-5. doi: 10.1016/j.jphs.2016.08.003. Epub 2016 Aug 12. PMID: 27569458.
9: Halliday M, Radford H, Sekine Y, Moreno J, Verity N, le Quesne J, Ortori CA, Barrett DA, Fromont C, Fischer PM, Harding HP, Ron D, Mallucci GR. 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. doi: 10.1038/cddis.2015.49. PMID: 25741597; PMCID: PMC4385927.
10: Sidrauski C, McGeachy AM, Ingolia NT, Walter P. The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly. Elife. 2015 Feb 26;4:e05033. doi: 10.7554/eLife.05033. PMID: 25719440; PMCID: PMC4341466.
