MCI-048

MCI-048 is a preclinical small molecule dual inhibitor of phosphodiesterase 10 (PDE10) and the β-catenin signaling pathway. Originally developed by ADT Pharmaceuticals and licensed by Anchiano Therapeutics in 2019, the compound is designed to target oncogenic pathways in solid tumors, including colorectal, lung, and pancreatic cancers. The mechanism involves the inhibition of PDE10, which leads to an increase in intracellular cyclic GMP (cGMP) levels. This elevation activates protein kinase G (PKG), which subsequently promotes the degradation of β-catenin, a key mediator of the Wnt signaling pathway often dysregulated in various malignancies. By suppressing β-catenin levels, MCI-048 aims to inhibit tumor cell proliferation and survival.