122nd General Meeting of the KCS

Type Poster Presentation
Area Medicinal Chemistry
Room No. Grand Ballroom
Time 10월 18일 (목요일) 11:00~12:30
Code MEDI.P-283
Subject A novel orally active inverse agonist of estrogen-related receptor gamma (ERRγ), DN200434, increase the susceptibility of radioiodine therapy against anaplastic thyroid cancer through upregulation of sodium iodide symporter (NIS) function
Authors Jina Kim, Jungwook Chin1,*, Sung Jin Cho1,*
Department of Chemistry, Daegu Gyeongbuk Medical Innovation Foundation, Korea
1New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation, Korea
Abstract New strategies to restore sodium iodide symporter (NIS) expression and function in anaplastic thyroid cancers (ATCs) that are refractory to radioiodine therapy are urgently required. Based on the structural motifs of GSK5182, we have successfully demonstrated the synthesis of compound libraries that are more selective against ERRγ inverse agonists with improved absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. Moreover, we have broadened the therapeutic scope of these compounds based on our findings that GSK5182 facilitates the responsiveness to radioiodine therapy by modulating NIS function in ATC cells via ERRγ and MAP kinase signaling pathway. Herein, we have validated the most promising ERRγ inverse agonist, DN200434, from our previous studies for its ability to enhance NIS protein function, which is a key protein for radioiodine therapy, and improve susceptibility to the therapy in in vitro/vivo ATC models.
E-mail jina@dgmif.re.kr