Structure, Function, and Pharmaceutical Ligands of 5-Hydroxytryptamine 2B Receptor

Since the first characterization of the 5-hydroxytryptamine 2B receptor (5-HT(2B)R) in 1992, significant progress has been made in 5-HT(2B)R research. Herein, we summarize the biological function, structure, and small-molecule pharmaceutical ligands of the 5-HT(2B)R. Emerging evidence has suggested that the 5-HT(2B)R is implicated in the regulation of the cardiovascular system, fibrosis disorders, cancer, the gastrointestinal (GI) tract, and the nervous system. Eight crystal complex structures of the 5-HT(2B)R bound with different ligands provided great insights into ligand recognition, activation mechanism, and biased signaling. Numerous 5-HT(2B)R antagonists have been discovered and developed, and several of them have advanced to clinical trials. It is expected that the novel 5-HT(2B)R antagonists with high potency and selectivity will lead to the development of first-in-class drugs in various therapeutic areas.