The new specific SMS2 small molecule inhibitor YE2 (CN202210213012.7) used in this study can attenuate macrophage M2 polarization by inhibiting the expression of IL4Rα and CSF1R on the plasma membrane and decreasing the infiltration of TAMs in pancreatic tumors, which changes the composition of the TME and suppresses tumor growth. This evidence concerns the gene SGMS2 and pancreatic neoplasm.