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Despite tremendous efforts, the clinical prognosis of pancreatic ductal adenocarcinoma ( PDAC ) remains disappointing. There is an urgent need to develop more effective treatment strategies to improve the prognosis of patients with  PDAC . In this study, we evaluate the anti‐ PDAC  effects of  LY ‐1816, a new multikinase inhibitor developed by us. In in vitro assays,  LY ‐1816 showed significant inhibitory effects on the proliferation, migration, and invasion of human  PDAC  cells, and induced  PDAC  cell apoptosis. Western blot analysis revealed that  LY ‐1816 markedly suppressed the Src signaling, and downregulated the expression of  FOSL 1;   FOSL 1  is an oncogene vulnerability in  KRAS ‐driven pancreatic cancer. In in vivo models of  PDAC  xenografts (Aspc‐1 and Bxpc‐3),  LY ‐1816 showed more potent antitumor activity than dasatinib and gemcitabine. Moreover, mice treated with  LY ‐1816 showed a much more significant survival advantage in a metastatic model of  PDAC  compared with those treated with vehicle, dasatinib, or gemcitabine. These results provide effective support for the subsequent clinical evaluation of  LY ‐1816 in the treatment of  PDAC .

Preclinical pharmacodynamic evaluation of a new Src/ FOSL 1 inhibitor, LY ‐1816, in pancreatic ductal adenocarcinoma