1597403-47-8
1597403-47-8 structure
- Name: ISRIB
- Chemical Name: Acetamide, N,N'-trans-1,4-cyclohexanediylbis[2-(4-chlorophenoxy)
- CAS Number: 1597403-47-8
- Molecular Formula: C22H24Cl2N2O4
- Molecular Weight: 451.343
- Catalog: Biochemical Inhibitor Apoptosis PERK inhibitor
- Create Date: 2018-12-06 17:55:06
- Modify Date: 2024-01-11 18:22:36
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ISRIB (trans-isomer) is a potent inhibitor of PERK with an IC50 of 5 nM.
| Name | Acetamide, N,N'-trans-1,4-cyclohexanediylbis[2-(4-chlorophenoxy) |
|---|---|
| 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) |
| Description | ISRIB (trans-isomer) is a potent inhibitor of PERK with an IC50 of 5 nM. |
|---|---|
| Related Catalog | |
| Target |
PERK:5 nM (IC50) |
| 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]. |
| 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]. |
| 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]. |
| 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]. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 719.0±60.0 °C at 760 mmHg |
| Molecular Formula | C22H24Cl2N2O4 |
| Molecular Weight | 451.343 |
| Flash Point | 388.6±32.9 °C |
| Exact Mass | 450.111328 |
| PSA | 76.66000 |
| LogP | 4.49 |
| Appearance | white solid |
| Vapour Pressure | 0.0±2.3 mmHg at 25°C |
| Index of Refraction | 1.603 |
| Storage condition | -20℃ |