SBI-364

SBI-364 is a first-in-class, potent small molecule competitive antagonist of the TGR5 receptor (also known as G protein-coupled bile acid receptor 1 or GPBAR1). Developed through a collaboration between Sanford Burnham Prebys and researchers at the Mayo Clinic, SBI-364 is designed to target the bile acid-TGR5 signaling axis, which is frequently dysregulated in cholangiocarcinoma (CCA) due to obstructive cholestasis. By inhibiting TGR5, the drug disrupts the establishment of an immunosuppressive tumor immune microenvironment (TIME). Specifically, SBI-364 treatment has been shown in preclinical models to reduce the accumulation of monocytic myeloid-derived suppressor cells (M-MDSCs) and interleukin-10-expressing macrophages, thereby alleviating the suppression of CD8+ T cells and reducing tumor burden in both intrahepatic and perihilar CCA models.