trans-ISRIB

• CAS: 1597403-47-8
• Catalog Number: ACM1597403478
• Category: Inhibitors
• Molecular Weight: 451.34
• Molecular Formula: C22H24Cl2N2O4
• Description: 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
• IUPAC Name: N,N'-((1r,4r)-cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide)
• Canonical SMILES: O=C(N[C@H]1CC[C@H](NC(COC2=CC=C(Cl)C=C2)=O)CC1)COC3=CC=C(Cl)C=C3
• 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)/t17-,18-
• InChI Key: HJGMCDHQPXTGAV-IYARVYRRSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 1597403-47-8 (trans-isomer); 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.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 58.55; H, 5.36; Cl, 15.71; N, 6.21; O, 14.18
• Exact Mass: 450.1113
• HS Tariff Code: 2934.99.9001
• 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/
• Shipping: 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.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).