Potential therapeutic applications of farnesoid X receptor (FXR) modulators

Abstract

Deorphanised in 1999 as a ligand inducible transcription factor responsive to bile acids, the farnesoid X receptor (FXR; NR1H4) soon turned out not to be ‘just another’ member of the superfamily of nuclear receptors, but has rapidly become the object of an intense research activity. This interest is motivated by the central role played by FXR in a variety of physiological processes and pathological conditions related to the control of bile acid and cholesterol homeostasis, and to lipid and energy metabolism. Facilitated by the early availability of both steroidal and nonsteroidal FXR activators, the characterisation of the physiological role of FXR has suggested several potential therapeutic applications associated with its modulation. Some of them, related to the role of FXR as a sensor for bile acids, have already been validated in in vivo models, whereas others, such as atherosclerosis and inflammation, are still in their speculative phase but endow a lot of promises. For these reasons, despite its youthfulness, FXR is a target of great relevance for both industrial and academic research. This article will review the whole patent production related to FXR and will give a perspective look at future developments.

Keywords::

• bile acid
• farnesoid X receptor (FXR)
• liver disease
• metabolic disease
• selective bile acid receptor modulator (SBARM)