fexaramine

Fexaramine is a synthetic, selective, and potent small molecule agonist of the farnesoid X receptor (FXR), a bile acid-activated nuclear receptor that regulates bile acid synthesis, conjugation, transport, and lipid metabolism in the liver and intestine[1][4][5]. Fexaramine was developed using combinatorial chemistry to have over 100-fold greater affinity for FXR than natural ligands[1][6]. When administered orally in preclinical studies (primarily in mice), it acts as a gut-restricted FXR agonist due to poor systemic absorption. This leads to selective activation of intestinal FXR pathways, resulting in increased fibroblast growth factor 15 (FGF15) production and metabolic improvements such as reduced weight gain, improved glucose control, browning of white adipose tissue, decreased inflammation, and increased insulin sensitivity[5][7]. Fexaramine has also been shown to inhibit osteoclast differentiation by downregulating NFATc1 signaling pathways via p38 MAPK/ERK/GSK3β modulation[4]. There are no clinical trials planned or ongoing for humans; all data are from preclinical animal models. The drug was originally developed by researchers at the Salk Institute for Biological Studies.