Design, synthesis and biological evaluation of quinazoline SOS1 inhibitors

Son of sevenless 1 (SOS1) is a vital guanine nucleotide exchange factor (GEFs) that activates rat sarcoma (Ras) protein in cells. SOS1 inhibitors can effectively inhibit the expression of downstream signaling pathways by blocking the interaction between SOS1 and Ras protein. Here, we designed and synthesized a series of quinazoline-based compounds, and conducted subsequent evaluations of their biological activities. Among them, the comparable compounds I-2 (IC50 = 20 nM, against SOS1) I-5 (IC50 = 18 nM, against SOS1) and I-10 (IC50 = 8.5 nM, against SOS1) have kinase activity equivalent to BAY-293 (IC50 = 6.6 nM, against SOS1), and I-10 also has cell activity equivalent to BAY-293, providing a theoretical reference for subsequent related researches on SOS1 inhibitors.

Automated summary

SOS1 is a crucial guanine nucleotide exchange factor that activates Ras protein in cells. We designed and synthesized a series of quinazoline-based compounds, and evaluated their biological activities. Among them, comparable compounds I-2 (IC50 = 20 nM), I-5 (IC50 = 18 nM), and I-10 (IC50 = 8.5 nM) have kinase activity equivalent to BAY-293 (IC50 = 6.6 nM) against SOS1, and I-10 also has cell activity equivalent to BAY-293, providing a theoretical reference for further research on SOS1 inhibitors.