SBI-115

SBI-115 may be used in cell proliferation and cyclic adenosine monophosphate (cAMP) assay to determine its effects on rodents with polycystic liver diseases and, to explore the mechanisms of TGR5 in inhibiting NLR family pyrin domain containing 3 (NLRP3) inflammasome under inflammatory conditions.

SBI-115, a specific TGR5/GPBAR1 antagonist, blocks agonist activation, inhibiting TGR5-Gαs-cAMP signaling and reducing intracellular cAMP in cystic cholangiocytes. This antagonism dose-dependently inhibits agonist-induced proliferation and reduces 3D cholangiocyte spheroid growth in vitro, enabling SBI-115 to attenuate Polycystic Liver Disease (PLD) pathology by modulating cAMP. Beyond PLD, SBI-115′s TGR5 modulation impacts inflammation by offsetting bile acid suppression of IL-1β/NLRP3 in macrophages and influences macrophage M2 polarization in non-small cell lung cancer, promoting antitumor immunity in vitro. Additionally, SBI-115 (1 µM) elevates triglycerides and reduces P-PPARA in fatty-degenerated hepatocytes, implicating TGR5 in lipid metabolism.