Background:

Fexaramine is a small molecule farnesoid X receptor (FXR) agonist with 100-fold increased affinity relative to natural compounds. IC50 value:Target:in vitro: In vitro treatment of CDCA or fexaramine elevated the SHP transcript level and occupancy on secretin promoter [1]. Fexaramine significantly enhanced osteoblastic differentiation through the upregulation of Runx2 and enhanced extracellular signal-regulated kinase (ERK) and β-catenin signaling [2]. By mimicking this tissue-selective effect, the gut-restricted FXR agonist fexaramine (Fex) robustly induces enteric fibroblast growth factor 15 (FGF15), leading to alterations in BA composition, but does so without activating FXR target genes in the liver [3].

参考文献:
[1]. Lam IP, et al. Bile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP). Am J Physiol Gastrointest Liver Physiol. 2009 Jul;297(1):G90-7.
[2]. Cho SW, et al. Positive regulation of osteogenesis by bile acid through FXR. J Bone Miner Res. 2013 Oct;28(10):2109-21.
[3]. Fang S, et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med. 2015 Feb;21(2):159-65.