Cis-ISRIB | CAS#548470-11-7 | Perk inhibitor

MedKoo Cat#: 555948 | Name: Cis-ISRIB

Description:

WARNING: This product is for research use only, not for human or veterinary use.

ISRIB, also known as cis-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.

Chemical Structure

Cis-ISRIB

CAS#548470-11-7 (cis-isomer)

Theoretical Analysis

MedKoo Cat#: 555948

Name: Cis-ISRIB

CAS#: 548470-11-7 (cis-isomer)

Chemical Formula: C22H24Cl2N2O4

Exact Mass: 450.1113

Molecular Weight: 451.34

Elemental Analysis: C, 58.55; H, 5.36; Cl, 15.71; N, 6.21; O, 14.18

Price and Availability

Size	Price	Availability
50mg	USD 550.00	2 Weeks
100mg	USD 950.00	2 Weeks
1g	USD 4,250.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

1597403-47-8 (trans-isomer) 548470-11-7 (cis-isomer)

Synonym

ISRIB; Cis-ISRIB; Cis ISRIB

IUPAC/Chemical Name

cis-2-(4-Chlorophenoxy)-N-[4-[[2-(4-chlorophenoxy)acetyl]amino]cyclohexyl]acetamide

InChi Key

HJGMCDHQPXTGAV-HDICACEKSA-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)/t17-,18+

SMILES Code

O=C(N[C@H]1CC[C@@H](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

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

ISRIB is a potent PERK inhibitor.

In vitro activity:

The administration of ISRIB significantly inhibited the apoptosis of NSCs, and the flow results were consistent with the in vivo results (Figures 5(d) and 5(e)). The above results suggest that ISRIB administration alleviates the apoptosis of NSCs induced by hypoxic exposure. Reference: Oxid Med Cell Longev. 2022 Sep 30;2022:3627026. https://pubmed.ncbi.nlm.nih.gov/36211820/

In vivo activity:

Alizarin red staining, calcium content, and ALP activity in the rat aorta were used to determine whether ISRIB could ameliorate VC progression. The increased calcium content and ALP activity in the calcified aorta were rescued by ISRIB treatment (Fig. 1B, C). Reference: Physiol Res. 2022 Jul 29;71(3):379-388. https://pubmed.ncbi.nlm.nih.gov/35616039/

	Solvent	mg/mL	mM
Solubility
	DMSO	15.0	0.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 451.34 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

Formulation protocol:

1. Zou Y, Yuan Z, Sun Y, Zhai M, Tan Z, Guan R, Aschner M, Luo W, Zhang J. Resetting Proteostasis of CIRBP with ISRIB Suppresses Neural Stem Cell Apoptosis under Hypoxic Exposure. Oxid Med Cell Longev. 2022 Sep 30;2022:3627026. doi: 10.1155/2022/3627026. PMID: 36211820; PMCID: PMC9546721. 2. 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. 3. Dong J, Jin S, Guo J, Yang R, Tian D, Xue H, Xiao L, Guo Q, Wang R, Xu M, Teng X, Wu Y. Pharmacological inhibition of eIF2alpha phosphorylation by integrated stress response inhibitor (ISRIB) ameliorates vascular calcification in rats. Physiol Res. 2022 Jul 29;71(3):379-388. doi: 10.33549/physiolres.934797. Epub 2022 May 26. PMID: 35616039; PMCID: PMC9470096. 4. Chang L, Liu X, Chen J, Liu H, Wang G, Wang G, Liao X, Shen X. Attenuation of Activated eIF2α Signaling by ISRIB Treatment After Spinal Cord Injury Improves Locomotor Function. J Mol Neurosci. 2022 Mar;72(3):585-597. doi: 10.1007/s12031-021-01920-9. Epub 2021 Oct 13. PMID: 34647267; PMCID: PMC8921087.

In vitro protocol:

In vivo protocol:

1. Dong J, Jin S, Guo J, Yang R, Tian D, Xue H, Xiao L, Guo Q, Wang R, Xu M, Teng X, Wu Y. Pharmacological inhibition of eIF2alpha phosphorylation by integrated stress response inhibitor (ISRIB) ameliorates vascular calcification in rats. Physiol Res. 2022 Jul 29;71(3):379-388. doi: 10.33549/physiolres.934797. Epub 2022 May 26. PMID: 35616039; PMCID: PMC9470096. 2. Chang L, Liu X, Chen J, Liu H, Wang G, Wang G, Liao X, Shen X. Attenuation of Activated eIF2α Signaling by ISRIB Treatment After Spinal Cord Injury Improves Locomotor Function. J Mol Neurosci. 2022 Mar;72(3):585-597. doi: 10.1007/s12031-021-01920-9. Epub 2021 Oct 13. PMID: 34647267; PMCID: PMC8921087.

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.