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  • 03월 02일 17시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제109회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Discovery of ERRgamma Inverse Agonist Eryvarin H and its SAR Study

2012년 3월 2일 16시 19분 04초
ORGN.P-967 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
4월 25일 (수요일) 18:00~21:00
저자 및
구자영, 박승범
서울대학교 화학부, Korea
Nuclear receptors are one of the important targets for various intracellular functions via regulating gene transcription. Orphan nuclear receptor has no identified ligands while it has similar structure with other identified receptors. Estrogen related receptor gamma is a third subtype receptor of ERRs and one of the orphan receptors. ERR gamma has various biological functions, which have been reported such as oxidative metabolism, suppressing cell proliferation and tumor growth of prostate cancer cells, and modulating cell proliferation and estrogen signaling in breast cancer. We found a inverse agonist, Eryvarin H, of ERR gamma from a number of natural compounds based on docking simulation. Eryvarin H is a known natural compound, which is one of the Eryvarin series isolated from the roots of plant Erythrina variegata. Then we synthesized Eryvarin H and its derivatives by our own methods via Suzuki-Miyaura cross-coupling reaction. Change of aryl groups by using different kinds of boronic acids gave us 12 different Eryvarin H derivatives. After synthesis of those compounds, we analyzed their inverse agonistic effect by using Gal4-fused ERRgamma LBD system emebedded on reporter gene assay. We discovered not only Eryvarin H but also its derivatives are inverse agonists of ERRgamma with comparable activity. Moreover, we could analyze the SAR pattern from the structural informations of 12 derivatives and their cell-based assay data. From this research, which is a natural compound based SAR approach assisted by protein-ligand docking, we can conclude that this work is a quite useful way to discover lead compounds for modulating selected target.