trans-ISRIB

Biological Activity

trans-ISRIB is a potent integrated stress response (ISR) inhibitor; reverses the effects of eIF2α phosphorylation (IC₅₀ = 5 nM) and restores cell translation capacity. Acts downstream of PERK, targeting interactions between eIF2α kinases and elF2B. Blocks ATF4 production without altering the IRE1 or ATF6 responses in vitro. Displays memory enhancement in hippocampus-dependent spatial and fear-associated learning in rodents. trans-ISRIB promotes survival of pluripotent stem cells in culture when used in combination with Chroman 1 (Cat. No. 7163), Emricasan (Cat. No. 7310), and Polyamine Supplement x1000 (lyophilized) (Cat. No. 7739), a combination known as CEPT. When used as part of the CEPT cocktail, trans-ISRIB improves survival of differentiated cells following cryopreservation. Brain penetrant.

Technical Data

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.

Background References

1. Inhibiting checkpoint kinase 1 protects bone from bone resorption by mammary tumor in a mouse model
   S Liu, Y Liu, K Minami, A Chen, Q Wan, Y Yin, L Gan, A Xu, N Matsuura, M Koizumi, Y Liu, S Na, J Li, H Nakshatri, BY Li, H Yokota
   Oncotarget, 2018;9(10):9364-9378.
2. Pharmacological brake-release of mRNA translation enhances cognitive memory.
   Sidrauski et al.
   Elife, 2013;2:e00498
3. Stress responses. Mutations in a translation initiation factor identify the target of a memory-enhancing compound.
   Sekine et al.
   Science, 2015;348:1027
4. Cell biology. Blocking stress response for better memory?
   Hinnebusch
   Science, 2015;348:967

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