In silico screening, synthesis, and biological evaluation of pyrazolopyrimidine-derived mTOR inhibitors for anticancer and senomorphic effects.

David Rysanek, Zofia Chrienova, Dorota Stary, Marek Bajda, Josef Novak, Pavla Vasicova, Jirina Kroupova, Rudolf Andrys, Adam Skarka, Erika Rousarova, Jan Capek, Tomas Rousar, Zoran Milovanovic, Jelica Grujic-Milanovic, Vesna Jacevic, Jayaprakash N Kolla, Martin Popr, Dominika Maurencova, Patrik Oleksak, Lukas Fresser, Kamil Kuca, Zdenek Hodny, Eugenie Nepovimova

Laboratory of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Videnska, Prague, 1083, 142 00, Czech Republic. [email protected]. · pubmed

Paper

Abstract

Cellular senescence is a stress-induced state characterized by irreversible cell cycle arrest. Senescent cells accumulate during aging and contribute to age-related diseases, including neurodegeneration, cancer, and type 2 diabetes mellitus. The mTOR signaling pathway plays a critical role in maintaining and regulating senescence-associated features.

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Research summary

The paper claims to identify and evaluate pyrazolopyrimidine-derived mTOR inhibitors that may have anticancer and senomorphic effects. The focus on mTOR signaling and its role in cellular senescence ties directly to mechanisms of aging and potential interventions that could address the root causes of age-related diseases.

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