SH-315

SH-315 is a highly selective, orally bioavailable small molecule inhibitor of phosphatidylinositol 3-kinase gamma (PI3Kγ) developed by the University of Michigan. It is designed to target the tumor immunosuppressive microenvironment by polarizing M2 tumor-associated macrophages (TAMs) to proinflammatory M1-like macrophages and reducing myeloid-derived suppressor cells (MDSCs), thereby enhancing cytotoxic CD8+ T cell activity. In preclinical models, SH-315 has demonstrated significant anti-tumor efficacy both as a monotherapy and in combination with paclitaxel or anti-PD-1 antibodies. Additionally, SH-315 has shown potential in treating autoimmune diseases, such as systemic lupus erythematosus, by reducing auto-antibodies, lymphadenopathy, and splenomegaly, and improving kidney function without causing hematological toxicity.