Trans Isrib
Cas No.: 1597403-47-8
What is Trans Isrib?
Trans Isrib (N,N’-trans-1,4-cyclohexanediylbis[2-(4-chlorofenoksy)acetamid]) is referred to as an Integrated Stress Response Inhibitor. In the literature it can also be referred to as Isrib (trans isomer) or trans-N,N′-(Cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide, trans-N,N′-1,4-Cyclohexanediylbis[2-(4-chlorophenoxy)-acetamide. This isomer exhibits up to 100 times more potent activity than the cis isomer.
Application of Trans Isrib
Trans Isrib compound can be used to improve memory, cognitive function. It can improve the body’s integrated stress response, as well as prevent a decline in protein synthesis. The compound has excellent pharmacokinetic properties, so it is quickly absorbed into the blood and crosses the blood-brain barrier, similar to L-dopa.
Mechanism of action
The compound Isrib ensures appropriate interactions between eIF2α and eIF2B, consequently reducing the effects of eIF2α phosphorylation. What does this mean? The eIF2 alpha protein is known to be blocked during a stress or pain response. It is an essential protein for the synthesis of other proteins, so disturbances in the levels of this compound have been linked m. in. With neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In addition, blocking of the eIF2 alpha protein is accompanied by m. in. Blocking of memories and deterioration of mental abilities.
The compound Isrib enables reversal of the inhibitory effect of stress on the activity of the eIF2 alpha protein. First – in animals given this compound, better perception of unpleasant stimuli and a significant improvement were observed mental functions . Second, animal studies have also shown that Isrib can restore memory function after post-traumatic brain injury.
In addition, in vitro studies showed that a composition of the compounds Trans Isrib, Emricasan, and Chroman-1 and polyamines (the combination was termed CEPT) promoted the survival of pluripotent stem cells. They are unique cells because they can be transformed into any cell of the body.
References:
- Sekine Y, Zyryanova A, Crespillo-Casado A, Fischer PM, Harding HP, Ron D. Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound. Science. 2015 May 29;348(6238):1027-30; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538794/
- 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; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667625/
- 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; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314867/
- Anand AA, Walter P. Structural insights into ISRIB, a memory-enhancing inhibitor of the integrated stress response. FEBS J. 2020 Jan;287(2):239-245; https://pubmed.ncbi.nlm.nih.gov/31550413/
