TUG-891 is a potent and selective agonist of the free fatty acid receptor 4 (FFA4/GPR120), which displays both potential opportunity and possible challenges to therapeutic agonism. Activation of human FFA4 by TUG-891 also resulted in rapid phosphorylation and internalization of the receptor. TUG-891 was also a potent agonist of mouse FFA4, but it showed only limited selectivity over mouse FFA1, complicating its use in vivo in this species.