Molecular docking-based virtual screening and dynamics simulation study of novel and potential SIRT7 inhibitors

In cancer cells, short for sirtuin (SIRT7) stabilizes the transformed state via its nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase activity. Epigenetic factor SIRT7 plays important roles in cancer biology, reversing cancer phenotypes and suppressing tumor growth when inactive. In the present study, we got the SIRT7 protein structure from Alpha Fold2 Database and performed structure-based virtual screening to develop specific SIRT7 inhibitors using the SIRT7 inhibitor 97,491 interaction mechanism. As candidates for specific SIRT7 inhibitors, compounds with high affinities to SIRT7 were chosen. ZINC000001910616 and ZINC000014708529, two of our leading compounds, showed strong interactions with SIRT7. Our MD simulation results also revealed that the 5-hydroxy-4H-thioxen-4-one group and terminal carboxyl group were critical groups responsible for interaction of small molecules with SIRT7. In our study, we demonstrated that targeting SIRT7 may offer novel therapeutic options for cancer treatment. Compounds ZINC000001910616 and ZINC000014708529 can serve as chemical probes to investigate SIRT7 biological functions and provide starting points for the development of novel therapeutics against cancers.