molecules of the month


oral nonbile acid FXR agonist

FGF15 induction in a BDL mouse modelSBDD

oral nonbile acid FXR agonist

J. Med. Chem.

Biocon-Bristol Myers Squibb Research and Development Center, Bangalore, IN

BMS-986399 structure
4 mins read

Context. BMS-986339 (BMS) is an oral farnesoid X receptor (FXR) agonist being developed for nonalcoholic steatohepatitis (NASH). Considered the master regulator of bile acid homeostasis, the nuclear receptor FXR may be an attractive target for diseases such as NASH, where bile acid dysregulation has been implicated. Currently, the only approved FXR agonist is Intercept’s bile acid-derived Obeticholic acid (Ocaliva), which is yet to be indicated for NASH, likely due to safety concerns; however, the company recently announced positive results from a Ph. III study. Other FXR agonists in clinical development include Novartis’ tropifexor (LJN452) and Gilead’s cilofexor, both of which are non-bile acid-derived. This is an interesting approach to indirectly treat the liver via influencing bile acid homeostasis in the…

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