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MedKoo Cat#: 530345 | Name: trans-ISRIB
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Description:

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

trans-ISRIB is an Integrated Stress Response Inhibitor. trans-ISRIB inhibits the eIF2α phosphorylation-mediated unfolded protein response following induction of ER stress (IC50 = 5 nM in a cell-reporter assay). ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly. ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly

Chemical Structure

trans-ISRIB
trans-ISRIB
CAS#1597403-47-8 (trans-isomer)

Theoretical Analysis

MedKoo Cat#: 530345

Name: trans-ISRIB

CAS#: 1597403-47-8 (trans-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 Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 350.00 Ready to ship
100mg USD 550.00 Ready to ship
200mg USD 950.00 Ready to ship
1g USD 2,450.00 Ready to Ship
2g USD 3,850.00 Ready to Ship
5g USD 5,950.00 Ready to Ship
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Related CAS #
1597403-47-8 (trans-isomer) 548470-11-7
Synonym
trans-ISRIB; transISRIB; trans ISRIB
IUPAC/Chemical Name
N,N'-((1r,4r)-cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide)
InChi Key
HJGMCDHQPXTGAV-IYARVYRRSA-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
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
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
Related CAS#548470-11-7
Biological target:
ISRIB is an integrated stress response (ISR) inhibitor that potently reverses the effects of eukaryotic initiation factor 2α (eIF2α) phosphorylation with IC50 of 5 nM.
In vitro activity:
Given that PERK phosphorylation was not diminished in ISRIB-treated, ER-stressed cells, next eIF2α phosphorylation was directly assessed. The levels of phosphorylated eIF2α were measured using an antiphospho-eIF2α antibody-based assay to quantify phosphorylation at serine 51 (see ‘Materials and methods’). Upon induction of ER stress by tunicamycin or thapsigargin, phosphorylation of eIF2α increased over time, reaching a fourfold and sevenfold increase after 120 min respectively. Unexpectedly, ISRIB did not block eIF2α phosphorylation under either of these ER stress-inducing conditions. On the contrary, 120 min after tunicamycin addition, ISRIB further increased the level of eIF2α phosphorylation, approaching that obtained with thapsigargin. ISRIB alone had no effect on eIF2α phosphorylation. These results indicate that ISRIB blocks effects downstream of PERK and eIF2α phosphorylation. Reference: Elife. 2013 May 28;2:e00498. https://pubmed.ncbi.nlm.nih.gov/23741617/
In vivo activity:
Treatment with ISRIB decreased the number of GFP+Siglec Flow monocyte-derived alveolar macrophages at day 14 after bleomycin in both young adult and old mice. To determine whether this reduction of monocyte-derived alveolar macrophages after treatment with ISRIB was attributable to reduced proliferation, mice were treated with EdU for 3 d before harvest. It was found that after administration of bleomycin, tissue-resident and monocyte-derived alveolar macrophages in old mice showed increased incorporation of EdU compared with young adult mice. The enhanced proliferation of tissue-resident and monocyte-derived alveolar macrophages in old mice 21 d after bleomycin was not observed in ISRIB-treated mice. Collectively, these results suggest that ISRIB either reduces the recruitment or inhibits factors required for the maintenance of monocyte-derived alveolar macrophages during bleomycin-induced fibrosis irrespective of age. Reference: Proc Natl Acad Sci U S A. 2021 May 18;118(20):e2101100118. https://pubmed.ncbi.nlm.nih.gov/33972447/
Solvent mg/mL mM
Solubility
DMSO 5.5 12.19
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.

Recalculate based on batch purity %
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. 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. Sidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR, Li H, Gamache K, Gallagher CM, Ang KK, Wilson C, Okreglak V, Ashkenazi A, Hann B, Nader K, Arkin MR, Renslo AR, Sonenberg N, Walter P. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife. 2013 May 28;2:e00498. doi: 10.7554/eLife.00498. PMID: 23741617; PMCID: PMC3667625. 3. . Watanabe S, Markov NS, Lu Z, Piseaux Aillon R, Soberanes S, Runyan CE, Ren Z, Grant RA, Maciel M, Abdala-Valencia H, Politanska Y, Nam K, Sichizya L, Kihshen HG, Joshi N, McQuattie-Pimentel AC, Gruner KA, Jain M, Sznajder JI, Morimoto RI, Reyfman PA, Gottardi CJ, Budinger GRS, Misharin AV. Resetting proteostasis with ISRIB promotes epithelial differentiation to attenuate pulmonary fibrosis. Proc Natl Acad Sci U S A. 2021 May 18;118(20):e2101100118. doi: 10.1073/pnas.2101100118. PMID: 33972447; PMCID: PMC8157939. 4. 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.
In vitro protocol:
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. Sidrauski C, Acosta-Alvear D, Khoutorsky A, Vedantham P, Hearn BR, Li H, Gamache K, Gallagher CM, Ang KK, Wilson C, Okreglak V, Ashkenazi A, Hann B, Nader K, Arkin MR, Renslo AR, Sonenberg N, Walter P. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife. 2013 May 28;2:e00498. doi: 10.7554/eLife.00498. PMID: 23741617; PMCID: PMC3667625.
In vivo protocol:
1. Watanabe S, Markov NS, Lu Z, Piseaux Aillon R, Soberanes S, Runyan CE, Ren Z, Grant RA, Maciel M, Abdala-Valencia H, Politanska Y, Nam K, Sichizya L, Kihshen HG, Joshi N, McQuattie-Pimentel AC, Gruner KA, Jain M, Sznajder JI, Morimoto RI, Reyfman PA, Gottardi CJ, Budinger GRS, Misharin AV. Resetting proteostasis with ISRIB promotes epithelial differentiation to attenuate pulmonary fibrosis. Proc Natl Acad Sci U S A. 2021 May 18;118(20):e2101100118. doi: 10.1073/pnas.2101100118. PMID: 33972447; PMCID: PMC8157939. 2. 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.
1: Xu C, He S, Zhu Y, Crasto G, Chen C, Clay ML, Lao YH, Leong KW. Vascular Organoid Generation from Human-Induced Pluripotent Stem Cells. J Vis Exp. 2024 Dec 13;(214). doi: 10.3791/67125. PMID: 39760384. 2: Clarke JWE, Messmer ML, Pilon J, Reding J, Thibault PA, Salapa HE, Levin MC. Dysfunctional RNA binding protein induced neurodegeneration is attenuated by inhibition of the integrated stress response. Biochim Biophys Acta Mol Basis Dis. 2025 Jan;1871(1):167562. doi: 10.1016/j.bbadis.2024.167562. Epub 2024 Nov 7. PMID: 39521193. 3: Williams D, Glasstetter LM, Jong TT, Chen T, Kapoor A, Zhu S, Zhu Y, Calvo R, Gehrlein A, Wong K, Hogan AN, Vocadlo DJ, Jagasia R, Marugan JJ, Sidransky E, Henderson MJ, Chen Y. High-throughput screening for small-molecule stabilizers of misfolded glucocerebrosidase in Gaucher disease and Parkinson's disease. Proc Natl Acad Sci U S A. 2024 Oct 15;121(42):e2406009121. doi: 10.1073/pnas.2406009121. Epub 2024 Oct 10. PMID: 39388267; PMCID: PMC11494340. 4: Xu S, Gierisch ME, Barchi E, Poser I, Alberti S, Salomons FA, Dantuma NP. Chemical inhibition of the integrated stress response impairs the ubiquitin- proteasome system. Commun Biol. 2024 Oct 8;7(1):1282. doi: 10.1038/s42003-024-06974-0. PMID: 39379572; PMCID: PMC11461528. 5: Isaac AR, Chauvet MG, Lima-Filho R, Wagner BA, Caroli BG, Leite REP, Suemoto CK, Nunes PV, De Felice FG, Ferreira ST, Lourenco MV. Defective regulation of the eIF2-eIF2B translational axis underlies depressive-like behavior in mice and correlates with major depressive disorder in humans. Transl Psychiatry. 2024 Oct 1;14(1):397. doi: 10.1038/s41398-024-03128-y. PMID: 39349438; PMCID: PMC11442801. 6: Yulyaningsih E, Suh JH, Fanok M, Chau R, Solanoy H, Takahashi R, Bakardjiev AI, Becerra I, Benitez NB, Chiu CL, Davis SS, Dowdle WE, Earr T, Estrada AA, Gill A, Ha C, Haddick PCG, Henne KR, Larhammar M, Leung AW, Maciuca R, Memarzadeh B, Nguyen HN, Nugent AA, Osipov M, Ran Y, Rebadulla K, Roche E, Sandmann T, Wang J, Lewcock JW, Scearce-Levie K, Kane LA, Sanchez PE. DNL343 is an investigational CNS penetrant eukaryotic initiation factor 2B activator that prevents and reverses the effects of neurodegeneration caused by the integrated stress response. Elife. 2024 Sep 17;12:RP92173. doi: 10.7554/eLife.92173. PMID: 39287504; PMCID: PMC11407769. 7: Jin R, Wang M, Shukla M, Lei Y, An D, Du J, Li G. J147 treatment protects against traumatic brain injury by inhibiting neuronal endoplasmic reticulum stress potentially via the AMPK/SREBP-1 pathway. Transl Res. 2024 Dec;274:21-34. doi: 10.1016/j.trsl.2024.08.007. Epub 2024 Sep 7. PMID: 39245209; PMCID: PMC11563885. 8: Watanabe T, Yasuda S, Kusakawa S, Kuroda T, Furukawa H, Futamura M, Shimizu S, Morishita A, Hata S, Koeda A, Komatsu K, Sato Y. Multisite studies for optimization of a highly efficient culture assay used for in vitro detection of residual undifferentiated human pluripotent stem cells intermingled in cell therapy products. Regen Ther. 2024 Jun 21;26:315-323. doi: 10.1016/j.reth.2024.06.007. PMID: 38983832; PMCID: PMC11231703. 9: Williams D, Glasstetter LM, Jong TT, Kapoor A, Zhu S, Zhu Y, Gehrlein A, Vocadlo DJ, Jagasia R, Marugan JJ, Sidransky E, Henderson MJ, Chen Y. Development of quantitative high-throughput screening assays to identify, validate, and optimize small-molecule stabilizers of misfolded β-glucocerebrosidase with therapeutic potential for Gaucher disease and Parkinson's disease. bioRxiv [Preprint]. 2024 Mar 27:2024.03.22.586364. doi: 10.1101/2024.03.22.586364. PMID: 38712038; PMCID: PMC11071283. 10: Ryu S, Weber C, Chu PH, Ernest B, Jovanovic VM, Deng T, Slamecka J, Hong H, Jethmalani Y, Baskir HM, Inman J, Braisted J, Hirst MB, Simeonov A, Voss TC, Tristan CA, Singeç I. Stress-free cell aggregation by using the CEPT cocktail enhances embryoid body and organoid fitness. Biofabrication. 2023 Dec 11;16(1). doi: 10.1088/1758-5090/ad0d13. PMID: 37972398. 11: Li M, Gao M, Jia M, Lu Y, Zhai Y, Lu H. ISRIB alleviates aging-associated brown fat UCP1 translational repression and thermogenic deficiency. Biochem Biophys Res Commun. 2023 Sep 17;673:179-186. doi: 10.1016/j.bbrc.2023.06.073. Epub 2023 Jun 24. PMID: 37393756. 12: Dhir N, Jain A, Sharma AR, Sharma S, Mahendru D, Patial A, Malik D, Prakash A, Attri SV, Bhattacharyya S, Das Radotra B, Medhi B. Rat BM-MSCs secretome alone and in combination with stiripentol and ISRIB, ameliorated microglial activation and apoptosis in experimental stroke. Behav Brain Res. 2023 Jul 9;449:114471. doi: 10.1016/j.bbr.2023.114471. Epub 2023 May 4. PMID: 37146724. 13: Wei W, Li Y, Wang C, Gao S, Zhao Y, Yang Z, Wang H, Gao Z, Jiang Y, He Y, Zhao L, Gao H, Yao X, Hu Y. Diterpenoid Vinigrol specifically activates ATF4/DDIT3-mediated PERK arm of unfolded protein response to drive non-apoptotic death of breast cancer cells. Pharmacol Res. 2022 Aug;182:106285. doi: 10.1016/j.phrs.2022.106285. Epub 2022 Jun 1. PMID: 35662627. 14: Lee DM, Seo MJ, Lee HJ, Jin HJ, Choi KS. ISRIB plus bortezomib triggers paraptosis in breast cancer cells via enhanced translation and subsequent proteotoxic stress. Biochem Biophys Res Commun. 2022 Mar 12;596:56-62. doi: 10.1016/j.bbrc.2022.01.082. Epub 2022 Jan 25. PMID: 35114585. 15: Lant JT, Kiri R, Duennwald ML, O'Donoghue P. Formation and persistence of polyglutamine aggregates in mistranslating cells. Nucleic Acids Res. 2021 Nov 18;49(20):11883-11899. doi: 10.1093/nar/gkab898. PMID: 34718744; PMCID: PMC8599886. 16: Lorenz NI, Sittig ACM, Urban H, Luger AL, Engel AL, Münch C, Steinbach JP, Ronellenfitsch MW. Activating transcription factor 4 mediates adaptation of human glioblastoma cells to hypoxia and temozolomide. Sci Rep. 2021 Jul 8;11(1):14161. doi: 10.1038/s41598-021-93663-1. PMID: 34239013; PMCID: PMC8266821. 17: Zhang T, Wu Y, Hu Z, Xing W, Kun LV, Wang D, Hu N. Small-Molecule Integrated Stress Response Inhibitor Reduces Susceptibility to Postinfarct Atrial Fibrillation in Rats via the Inhibition of Integrated Stress Responses. J Pharmacol Exp Ther. 2021 Sep;378(3):197-206. doi: 10.1124/jpet.121.000491. Epub 2021 Jul 2. PMID: 34215702. 18: Tang X, Uhl S, Zhang T, Xue D, Li B, Vandana JJ, Acklin JA, Bonnycastle LL, Narisu N, Erdos MR, Bram Y, Chandar V, Chong ACN, Lacko LA, Min Z, Lim JK, Borczuk AC, Xiang J, Naji A, Collins FS, Evans T, Liu C, tenOever BR, Schwartz RE, Chen S. SARS-CoV-2 infection induces beta cell transdifferentiation. Cell Metab. 2021 Aug 3;33(8):1577-1591.e7. doi: 10.1016/j.cmet.2021.05.015. Epub 2021 May 19. PMID: 34081913; PMCID: PMC8133495. 19: Watanabe S, Markov NS, Lu Z, Piseaux Aillon R, Soberanes S, Runyan CE, Ren Z, Grant RA, Maciel M, Abdala-Valencia H, Politanska Y, Nam K, Sichizya L, Kihshen HG, Joshi N, McQuattie-Pimentel AC, Gruner KA, Jain M, Sznajder JI, Morimoto RI, Reyfman PA, Gottardi CJ, Budinger GRS, Misharin AV. Resetting proteostasis with ISRIB promotes epithelial differentiation to attenuate pulmonary fibrosis. Proc Natl Acad Sci U S A. 2021 May 18;118(20):e2101100118. doi: 10.1073/pnas.2101100118. PMID: 33972447; PMCID: PMC8157939. 20: Chen Y, Tristan CA, Chen L, Jovanovic VM, Malley C, Chu PH, Ryu S, Deng T, Ormanoglu P, Tao D, Fang Y, Slamecka J, Hong H, LeClair CA, Michael S, Austin CP, Simeonov A, Singeç I. A versatile polypharmacology platform promotes cytoprotection and viability of human pluripotent and differentiated cells. Nat Methods. 2021 May;18(5):528-541. doi: 10.1038/s41592-021-01126-2. Epub 2021 May 3. PMID: 33941937; PMCID: PMC8314867.