121st General Meeting of the KCS

Type Poster Presentation
Area Medicinal Chemistry
Room No. Event Hall
Time 4월 19일 (목요일) 11:00~12:30
Code MEDI.P-599
Subject Functional selectivity of Tetrahydroazepine derivatives in G-protein/ β-arrestin signaling pathways
Authors Jieon Lee, Youngjae Kim1, Hyunah Choo2,*
Center for Neuromedicine, Korea Institute of Science and Technology, Korea
1Department of Chemistry, Yonsei University, Korea
2Korea Institute of Science and Technology, Korea
Abstract 5-HT7 receptor (5-HT7R) is the most recently identified member of the family of 5-HT receptors (5-HTRs) and has been cloned from a variety of species, including human and rat. 5-HT7R is localized within CNS such as hypothalamus, pontine nuclei, dorsal raphe nucleus, basal forebrain, and hippocampus. Important roles for the central 5-HT7 receptor have been investigated in the regulation of the sleep-wake cycle and circadian rhythm. 5-HT7R belongs to the family of G protien coupled receptors(GPCRs) and is shown to be positively coupled to adenylate cyclase via Gs-proteins. Apart from canonical G protein mediated signaling, GPCRs also activate noncanonical G protein-independent pathways, frequently mediated by β-arrestin. The process by which GPCR ligands differentially modulate signal transduction pathways is a phenomenon known as “functional selectivity”. The discovery of ligands with functional selectivity profiles will be useful for elucidating the key signal transduction pathways essential for both the therapeutic actions and the side effects of drugs. Until now, there has not been reported how 5-HT7 agonists or antagonists in G-protein signaling pathway will act in β-arrestin signaling pathway. Herein, we designed and synthesized tetrahydroazepine derivatives of which functional assay was also performed. The results will be presented in details.
E-mail h16508@kist.re.kr