Docking analysis provide structural insights to design novel ligands that target PKM2 and HDC8 with potential use for cancer therapy

The search of protein targets involved in cancer has gained importance in the later years since cancer remains of the leading causes of death in the world. Histone deacetylase 8 (HDC8) play a key role in epigenetic regulation in cancer diseases. In addition, pyruvate kinase (PKM2) has been also identified overexpressed in cancer diseases.Since both targets are involved in cancer diseases, their crystal structures are available and their chemical moiety pharmacophores have been identified, we propose to design some drugs that could target both proteins. These bi-target compounds were submitted to theoretically ADMET analysis and docking studies in order to select the best-scored compounds. From the docking studies, it was possible to elucidate the residues that are involved in their binding recognition of PKM2 and HDC8. Such knowledge is of relevant importance since it will permit the design of new compounds that could effectively target and modulate these proteins that are critically involved in the pathology of cancer. Finally, the computational techniques permitted to select the most favourable compounds (A_4, A_7, A_10, D_6 and D_17), bringing new therapeutic perspectives by using these potential drugs.