C16 (drug) explained

C16 (PKRi, GW 506033X) is a drug which acts as a selective inhibitor of the enzyme double-stranded RNA-dependent protein kinase (PKR). It has been shown to effectively inhibit PKR function in vivo and has neuroprotective and nootropic effects in animal studies.^{[1] [2] [3] [4] [5] [6] [7] [8]}

See also

• S-17092

Notes and References

1. Jammi NV, Whitby LR, Beal PA . Small molecule inhibitors of the RNA-dependent protein kinase . Biochemical and Biophysical Research Communications . 308 . 1 . 50–57 . August 2003 . 12890478 . 10.1016/s0006-291x(03)01318-4 .
2. Shimazawa M, Hara H . Inhibitor of double stranded RNA-dependent protein kinase protects against cell damage induced by ER stress . Neuroscience Letters . 409 . 3 . 192–195 . December 2006 . 17055645 . 10.1016/j.neulet.2006.09.074 . 43133290 .
3. Ingrand S, Barrier L, Lafay-Chebassier C, Fauconneau B, Page G, Hugon J . The oxindole/imidazole derivative C16 reduces in vivo brain PKR activation . FEBS Letters . 581 . 23 . 4473–4478 . September 2007 . 17761171 . 10.1016/j.febslet.2007.08.022 . free .
4. Chen HM, Wang L, D'Mello SR . A chemical compound commonly used to inhibit PKR,, protects neurons by inhibiting cyclin-dependent kinase . The European Journal of Neuroscience . 28 . 10 . 2003–2016 . November 2008 . 19046382 . 3320856 . 10.1111/j.1460-9568.2008.06491.x .
5. Couturier J, Morel M, Pontcharraud R, Gontier V, Fauconneau B, Paccalin M, Page G . Interaction of double-stranded RNA-dependent protein kinase (PKR) with the death receptor signaling pathway in amyloid beta (Abeta)-treated cells and in APPSLPS1 knock-in mice . The Journal of Biological Chemistry . 285 . 2 . 1272–1282 . January 2010 . 19889624 . 2801255 . 10.1074/jbc.M109.041954 . free .
6. Zhu PJ, Huang W, Kalikulov D, Yoo JW, Placzek AN, Stoica L, Zhou H, Bell JC, Friedlander MJ, Krnjević K, Noebels JL, Costa-Mattioli M . 6 . Suppression of PKR promotes network excitability and enhanced cognition by interferon-γ-mediated disinhibition . Cell . 147 . 6 . 1384–1396 . December 2011 . 22153080 . 3569515 . 10.1016/j.cell.2011.11.029 .
7. Hwang KD, Bak MS, Kim SJ, Rhee S, Lee YS . Restoring synaptic plasticity and memory in mouse models of Alzheimer's disease by PKR inhibition . Molecular Brain . 10 . 1 . 57 . December 2017 . 29233183 . 5727890 . 10.1186/s13041-017-0338-3 . free .
8. Gal-Ben-Ari S, Barrera I, Ehrlich M, Rosenblum K . PKR: A Kinase to Remember . Frontiers in Molecular Neuroscience . 11 . 480 . 2018 . 30686999 . 6333748 . 10.3389/fnmol.2018.00480 . free .