5-HT_2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology.

ABSTRACT: Drugs frequently require interactions with multiple targets-via a process known as polypharmacology-to achieve their therapeutic actions. Currently, drugs targeting several serotonin receptors, including the 5-HT_2C receptor, are useful for treating obesity, drug abuse, and schizophrenia. The competing challenges of developing selective 5-HT_2C receptor ligands or creating drugs with a defined polypharmacological profile, especially aimed at G protein-coupled receptors (GPCRs), remain extremely difficult. Here, we solved two structures of the 5-HT_2C receptor in complex with the highly promiscuous agonist ergotamine and the 5-HT_2A-C receptor-selective inverse agonist ritanserin at resolutions of 3.0 Å and 2.7 Å, respectively. We analyzed their respe

SUBMITTER: Peng Y 

PROVIDER: S-EPMC6309861 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature