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An achievement that was deemed impossible has successfully become accomplished. For the first time in history, DNA can be edited. One of the goals is to be able to get rid of genetic diseases. This whole concept in genomic science has opened up a whole new revolutionary way of dealing with such critical health issues. There is a possibility that illnesses that were once incurable have a chance to be curable.

MedlinePlus provides a definition and states that a collection of tools known as genome editing, or gene editing, allows researchers to alter an organism’s DNA. These technologies enable the addition, deletion, or modification of genetic material at specific genomic regions. A person’s DNA can be altered through gene editing to fix mistakes that lead to illnesses.

CRISPR-Cas9, short for CRISPR-associated protein 9 and clustered regularly interspaced short palindromic repeats, is a well-known example as one of the approaches used and developed by scientists to edit DNA. The scientific community is very excited about the CRISPR-Cas9 system since it is more accurate, efficient, quicker, and less expensive than existing genome editing techniques.

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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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