Design and screening of SGK1, Src dual inhibitors using pharmacophore models, molecular docking, and molecular dynamics simulation

Serum and glucocorticoid-regulated protein kinase 1 (SGK1) that can promote the growth of tumor cells is highly expressed in many tumors. Sarcoma gene (Src), a class of oncogenes, plays an important role in the pathogenesis of cancer and is an important kinase in tumor cell expression pathways. Research has shown that SGK1, as a key regulator, is involved in Src-induced tumor formation, and tumor progression can be inhibited by inhibiting SGK1/Src in combination. In this study, SGK1/Src dual inhibitors were designed by computer-aided drug design. Seven million molecules were screened via the pharmacophore model and molecular docking. Finally, 6 compounds were selected. The results of molecular dynamics simulation of compound 1 showed that it has good binding stability to both receptors. According to the binding site of compound 1 with two receptors, corresponding modifications were made, and 6 novel designed compounds were obtained. The docking energies of the novel designed compounds were lower than that of compound 1.