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Department of Chemistry Faculty of Sc... 1 Department of Genome Integrity Instit... 1 Department of Neurology University Ho... 1 Department of Physicochemical Drug An... 1 Doctoral School of Medical and Health... 1 Faculty of Medicine in Hradec Králové... 1 Laboratory of Immunological and Tumor... 1
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Department of Chemistry Faculty of Sc... 1 Department of Genome Integrity Instit... 1 Department of Neurology University Ho... 1 Department of Physicochemical Drug An... 1 Doctoral School of Medical and Health... 1 Faculty of Medicine in Hradec Králové... 1 Laboratory of Immunological and Tumor... 1
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NLK
Directory of Open Access Journals
od 2009
Free Medical Journals
od 2009
PubMed Central
od 2009
Europe PubMed Central
od 2009
ProQuest Central
od 2009-07-30
Open Access Digital Library
od 2009-01-01
Open Access Digital Library
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Health & Medicine (ProQuest)
od 2009-07-30
ROAD: Directory of Open Access Scholarly Resources
od 2009
PubMed
36561137
DOI
10.3389/fnagi.2022.1048260
Knihovny.cz E-zdroje
To date, the most studied drug in anti-aging research is the mTOR inhibitor - rapamycin. Despite its almost perfect anti-aging profile, rapamycin exerts one significant limitation - inappropriate physicochemical properties. Therefore, we have decided to utilize virtual high-throughput screening and fragment-based design in search of novel mTOR inhibiting scaffolds with suitable physicochemical parameters. Seven lead compounds were selected from the list of obtained hits that were commercially available (4, 5, and 7) or their synthesis was feasible (1, 2, 3, and 6) and evaluated in vitro and subsequently in vivo. Of all these substances, only compound 3 demonstrated a significant cytotoxic, senolytic, and senomorphic effect on normal and cancerous cells. Further, it has been confirmed that compound 3 is a direct mTORC1 inhibitor. Last but not least, compound 3 was found to exhibit anti-SASP activity concurrently being relatively safe within the test of in vivo tolerability. All these outstanding results highlight compound 3 as a scaffold worthy of further investigation.
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Po ukončení testovacího provozu bude odkaz přesměrován adresu produkční verze portálu Medvik.