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María Ángel García Chaves

Figure 5. PKR is a molecular target of both anticancer drugs, the chemotherapeutic 5-Fluorouracil and the novel compound
Bozepinib. 5-FU and Bozepinib activates PKR inducing cancer cell death by apoptosis. Whereas 5-FU induces PKR activation in a p53-
independent manner, Bozepinib does not activate p53. Both drugs synergized its antitumour effect in combination with IFNa.. Moreover
Bozepinib is able to induce atophagy and senescense in cancer cells in combination with IFNa. In addition Bozepinib inhibits both mamo
and colono-spheres formation regulating genes related to stem properties such as c-MYC, ß-CATENIN, SOX2 and GLI-3 hedgehog-
signaling repressor.

Figure 6. Bozepinib structure [(RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1- benzoxazepin-3-yl]-9H-purine].

We have previously published Bozepinib structure in Lopez-Cara et al. (157).

4.2. PKR as a molecular target in neurodegenerative (Aß) peptide, neurofibrillary tangles made of
diseases hyperphosphorylated T-tau protein, neuronal loss, and
neuroinflammation, where the apoptotic death
Alzheimer's disease (AD) is a neurodegenerative
disorder marked by senile plaques composed of amyloid-ß characterises most of affected neurons. In 2002,
histological methods showed that activated PKR was

158 @Real Academia Nacional de Farmacia. Spain