ISRIB is a small molecule with a bicyclic scaffold supporting studies of conformational rigidity and heterocycle-driven interactions. Its structure enables investigation of allosteric modulation, folding perturbation, and protein-ligand dynamics. Researchers employ it in exploring regulatory mechanisms and synthetic design principles. The compound's physicochemical profile supports extensive structural characterization.
CAT No: PI-015
CAS No:548470-11-7
Synonyms/Alias:ISRIB;1597403-47-8;trans-ISRIB;548470-11-7;ISRIB (trans-isomer);1597403-48-9;N,N'-(cis-Cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide);ISRIB trans-isomer;2-(4-chlorophenoxy)-N-[4-[[2-(4-chlorophenoxy)acetyl]amino]cyclohexyl]acetamide;N,N'-(Cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide);Integrated Stress Response inhibitor;N,N'-trans-1,4-cyclohexanediylbis[2-(4-chlorophenoxy)acetamide];Acetamide, N,N'-trans-1,4-cyclohexanediylbis[2-(4-chlorophenoxy)-;2-(4-chlorophenoxy)-N-[(1s,4s)-4-[2-(4-chlorophenoxy)acetamido]cyclohexyl]acetamide;2-(4-chlorophenoxy)-N-{4-[2-(4-chlorophenoxy)acetamido]cyclohexyl}acetamide;N,N'-(trans-cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide);2-(4-chloranylphenoxy)-~{N}-[4-[2-(4-chloranylphenoxy)ethanoylamino]cyclohexyl]ethanamide;cis-ISRIB;N,N'-((1r,4r)-cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide);C22H24Cl2N2O4;N,N'-trans-1,4-Cyclohexanediylbis[2-(4-chlorophenoxy)acetamide]; SMDC 750213;C7B;MFCD27952932;cis-ISRIB;ISRIB;ISRIB (cis-isomer);ISRIB?;S6SZR97SBZ;Oprea1_706389;AK-968/13065027;CHEMBL4303573;SCHEMBL16082980;SCHEMBL16082988;SCHEMBL16083047;EX-A298;CHEBI:232338;DTXSID601045380;GLXC-03636;HMS3887M19;SMDC750213;BCP10786;BCP23947;ISRIB, >=98% (HPLC);SMDC-750213;XNC40347;HY-12495A;s7400;STK435431;AKOS003300916;AKOS025142075;AKOS030633038;CCG-269245;2-(4-chlorophenoxy)-N-(4-{[(4-chlorophenoxy)acetyl]amino}cyclohexyl)acetamide;NCGC00384174-11;NCGC00384174-13;NCGC00389802-01;AC-35228;AS-16593;AS-55833;BI179448;DA-28222;DA-54475;DS-19940;CS-0029263;CS-0187553;S0706;C73020;BRD-K12826175-001-02-4;N,N'-cyclohexane-1,4-diylbis[2-(4-chlorophenoxy)acetamide];N,Na(2)-trans-1,4-Cyclohexanediylbis[2-(4-chlorophenoxy)acetamide];2-(4-chlorophenoxy)-N-[(1r,4r)-4-[2-(4-chlorophenoxy)acetamido]cyclohexyl]acetamide;
Chemical Name:2-(4-chlorophenoxy)-N-[4-[[2-(4-chlorophenoxy)acetyl]amino]cyclohexyl]acetamide
ISRIB (Integrated Stress Response Inhibitor) is a small-molecule compound recognized for its ability to modulate the integrated stress response (ISR), a critical cellular pathway that regulates protein synthesis in response to diverse stress signals. Functioning as a selective activator of eIF2B, ISRIB counteracts the translational repression triggered by eIF2α phosphorylation, thereby restoring global protein synthesis under stress conditions. Its unique mechanism of action and specificity for the ISR pathway have made it a valuable tool for dissecting the molecular underpinnings of cellular stress responses, translational control, and related signaling networks. As such, ISRIB is widely employed in biochemical and molecular biology research to probe the dynamics of stress adaptation and translational regulation in eukaryotic cells.
Cellular Stress Response Research: ISRIB is extensively utilized to investigate the molecular mechanisms underlying the integrated stress response. By selectively antagonizing eIF2α phosphorylation-mediated translational inhibition, it enables researchers to dissect the downstream effects of ISR activation on gene expression, protein synthesis, and cellular homeostasis. Studies employing this compound have elucidated the role of stress granule dynamics, unfolded protein response signaling, and adaptive versus maladaptive responses to ER stress, providing critical insights into how cells maintain proteostasis under adverse conditions.
Translational Regulation Studies: The compound serves as a powerful experimental tool for examining the regulation of mRNA translation during cellular stress. By restoring eIF2B activity, ISRIB allows for the controlled manipulation of protein synthesis rates in vitro and in cell-based systems. This capability is particularly valuable for researchers aiming to distinguish between global and selective translational responses, identify ISR-sensitive transcripts, and characterize the interplay between translation initiation factors and stress-responsive pathways.
Neurobiology and Memory Research: In neuroscience, ISRIB has been employed to probe the effects of translational control on synaptic plasticity, memory formation, and cognitive processes. Its ability to modulate protein synthesis in neural cells provides a mechanistic window into the impact of ISR on neuronal function and plasticity. Experimental applications include studies of learning and memory circuits, synaptic remodeling, and the cellular basis of cognitive adaptation to stress.
Chemical Biology and Drug Discovery: As a well-characterized modulator of eIF2B, ISRIB is frequently used in chemical biology to validate targets within the ISR pathway and to screen for novel small molecules with similar or complementary activity. Its defined mechanism enables high-confidence assays in structure-activity relationship studies, target engagement analyses, and the development of next-generation ISR modulators. This makes it an important reference compound for both target validation and lead optimization efforts in translational research.
Proteostasis and Disease Modeling: ISRIB is also applied in the context of cellular models that mimic proteostasis imbalance, such as those induced by misfolded protein accumulation or oxidative stress. By alleviating ISR-mediated translational arrest, it facilitates the study of protein quality control mechanisms, stress adaptation, and the cellular consequences of disrupted proteostasis. This application is particularly relevant for research into neurodegenerative disorders, metabolic stress, and other conditions where ISR activation plays a pivotal role in cellular pathology.
3. Implications of ligand-receptor binding kinetics on GLP-1R signalling
4. Urinary Metabolites Associated with Blood Pressure on a Low-or High-Sodium Die
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