In vitro activity: CPDA [N-[4-(4-chlorobenzyloxy)pyridin-2-yl]-2-(2,6-difluorophenyl)- acetamide] is a novel potent inhibitor of SHIP2 [SH2-containing 5'-inositol phosphatase 2] that can effectively ameliorate insulin resistance in 3T3-L1 adipocytes. CPDA was identified using in-silico ligand-based drug design (LBDD) in an attempt to identify inhibitors of SH2-containing 5'-inositol phosphatase 2 (SHIP2), which is implicated in insulin-resistant type 2 diabetes. Among the compounds synthesized, (CPDA, 4a) was identified as a potent SHIP2 inhibitor. CPDA was found to enhance in vitro insulin signaling through the Akt pathway more efficiently than the previously reported SHIP2 inhibitor AS1949490, and ameliorated abnormal glucose metabolism in diabetic (db/db) mice.

Kinase Assay: CPDA was found to enhance insulin signaling.

Cell Assay: