By pretreatment of YE2, the M2 polarization induced by PDAC-CM or IL-4 in BMDMs and THP-1 cells was significantly inhibited, and the in vivo efficacy was consistent with that of SMS2 deficiency, suggesting the potential application of the SMS2-targeting small molecule inhibitor YE2 in pancreatic cancer treatment. The gene discussed is SGMS2; the disease is familial pancreatic carcinoma.