Introduction：Basic information about CAS 1597403-47-8|ISRIB, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | ISRIB |
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| CAS Number | 1597403-47-8 | Molecular Weight | 451.343 |
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| Density | 1.3±0.1 g/cm3 | Boiling Point | 719.0±60.0 °C at 760 mmHg |
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| Molecular Formula | C22H24Cl2N2O4 | Melting Point | / |
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| MSDS | / | Flash Point | 388.6±32.9 °C |
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Names
| Name | Acetamide, N,N'-trans-1,4-cyclohexanediylbis[2-(4-chlorophenoxy) |
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| Synonym | More Synonyms |
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ISRIB BiologicalActivity
| Description | ISRIB (trans-isomer) is a potent inhibitor of PERK with an IC50 of 5 nM. |
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| Related Catalog | Signaling Pathways >>Cell Cycle/DNA Damage >>PERKResearch Areas >>Neurological Disease |
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| Target | PERK:5 nM (IC50) |
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| In Vitro | Trans-ISRIB is 100-fold more potent (IC50=5 nM) than cis-ISRIB (IC50= 600 nM), indicating that the compound’s interaction with its cellular target is stereospecific. ISRIB reduces the viability of cells subjected to PERK-activation by chronic endoplasmic reticulum stress[1]. ISRIB substantially reverses the translational effects elicited by phosphorylation of eIF2α and induces no major changes in translation or mRNA levels in unstressed cells. eIF2α phosphorylation-induced stress granule (SG) formation is blocked by ISRIB[2]. |
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| In Vivo | ISRIB increases long-term memory in rodents. ISRIB-treated mice display significant enhancement in spatial and fear-associated learning. ISRIB displays a half-life in plasma of 8 hr and readily crossed the blood-brain barrier, quickly equilibrating with the central nervous system[1]. |
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| Cell Assay | U2OS cells are plated on 96-well plates and left to recover overnight. Cells are treated with either with 2 µg/ml tunicamycin or 100 nM thapsigargin in the presence or absence of 100 nM ISRIB or with ISRIB alone for the indicated and the level of eIF2α phosphorylation is determined[1]. |
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| Animal Admin | Mice: Intra-peritoneal (ip) route of administration is performed on 6-7 wk old female CD-1 mice. Animals receives a single, 5 mg/kg dose in groups of three mice/compound/route of administration. ISRIB is dissolved in DMSO then diluted 1:1 in Super-Refined PEG 400. Blood (80 μL) is collected from the saphenous vein at intervals post-dosing (20 min, 1 hr, 3 hr, 8 hr, 24 hr) in EDTA containing collection tubes and plasma is prepared for analysis. Compounds are detected by time-of-flight mass spectroscopy[1]. |
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| References | [1]. Sidrauski C, et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife. 2013 May 28;2:e00498. [2]. Sidrauski C, et al. The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stressgranule assembly. Elife. 2015 Feb 26;4. doi: 10.7554/eLife.05033. |
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Chemical & Physical Properties
| Density | 1.3±0.1 g/cm3 |
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| Boiling Point | 719.0±60.0 °C at 760 mmHg |
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| Molecular Formula | C22H24Cl2N2O4 |
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| Molecular Weight | 451.343 |
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| Flash Point | 388.6±32.9 °C |
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| Exact Mass | 450.111328 |
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| PSA | 76.66000 |
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| LogP | 4.49 |
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| Appearance of Characters | white solid |
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| Vapour Pressure | 0.0±2.3 mmHg at 25°C |
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| Index of Refraction | 1.603 |
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| InChIKey | HJGMCDHQPXTGAV-UHFFFAOYSA-N |
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| SMILES | O=C(COc1ccc(Cl)cc1)NC1CCC(NC(=O)COc2ccc(Cl)cc2)CC1 |
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| Storage condition | -20℃ |
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Synonyms
| N,N'-1,4-Cyclohexanediylbis[2-(4-chlorophenoxy)acetamide] |
| Acetamide, N,N'-trans-1,4-cyclohexanediylbis[2-(4-chlorophenoxy)- |
| N,N'-trans-1,4-Cyclohexanediylbis[2-(4-chlorophenoxy)acetamide] |
| Acetamide, N,N'-1,4-cyclohexanediylbis[2-(4-chlorophenoxy)- |
| ISRIB |
| trans-ISRIB |
| ISRIB (trans-isomer) |
