123rd General Meeting of the KCS

Type Poster Presentation
Area Medicinal Chemistry
Room No. Exhibition Hall 2
Time 4월 18일 (목요일) 11:00~12:30
Code MEDI.P-399
Subject Discovery of Potent, Selective, and Orally Bioavailable Estrogen-Related Receptor‑γ Inverse Agonists
Authors Jina Kim, Jungwook Chin*, Sung Jin Cho*
New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation, Korea
Abstract ERRγ is abundantly expressed in various tissues associated with the CNS, circadian clock, and basal metabolic function; thus, it not only regulates ion homeostasis in related tissues but also controls metabolic processes such as mitochondrial biogenesis and hepatic gluconeogenesis. We synthesized potent, selective and orally bioavailable ERRγ inverse agonists and evaluated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that not only were shown to be highly selective inverse agonists for ERRγ but also exhibited enhanced pharmacokinetic profile compared with GSK5182. We observed a significant increase of fully glycosylated NIS protein, key protein for radioiodine therapy in anaplastic thyroid cancer (ATC), in DN201000-treated CAL62 cells, which indicated that these compounds could be promising enhancers for restoring NIS protein function in ATC cells. Thus, DN201000 possess advantageous druglike properties and can be used to potentially treat various ERRγ-related disorders.
E-mail jina@dgmif.re.kr