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学术报告——De-orphaning Nuclear Receptors for Drug Discovery

题 目:De-orphaning Nuclear Receptors for Drug Discovery
报告人:Zhong Zhong, Ph.D.
Senior Director of Discovery, Regenerative Medicine
单 位:GlaxoSmithKline
时 间: 2012.9.21.(本周五) 上午 9:30
地 点: 强磁场中心 201 会议室
报告人简介:钟忠 博士,现任葛兰素史克公司再生医学部高级总监,曾任该公司上海研发中心药物发现技术部高级总监四年, 推动神经退行性疾病药物的筛选及干细胞平台的建立。他多年从事高通量药物筛选平台的建设和技术发展,曾主持 2002年在美国旧金山和瑞士苏黎世举办的IBC国际细胞筛选模型年会,2010年SBS在上海首次创办的生物筛选年会。他还被邀在Keystone Conference, ISSCR, Singapore Stem Cell Society等学会上作演讲。目前担任“Assay Drug Development Technologies” ,“Current Chemical Genomics” 杂志的编委, 实验室自动化与筛选协会(SLAS)国际顾问。钟忠博士就读于复旦大学基因工程专业,获得洛克菲洛大学细胞生物学博士,攻读哥伦比亚大学博士后期间获得生命科学基金会奖学金。钟忠博士在《Science》、《Proc. Natl. Acad. Sci. USA》、《Cell》、《Journal of Biological Chemistry》等国外学术杂志上发表论文近30篇,并著有十多项专利。曾任强生药品研究所的高级科学家、Cell & Molecular Technologies Inc 公司的药物发现技术副总裁、Invitrogen公司的药物开发产品总监。

报告摘要:In a screen for small molecule inhibitors of RORγ, we fortuitously discovered that a class of aryl amide compounds behaved as functional activators of the IL-17 reporter in Jurkat cells. Three of these compounds were selected for further analysis and found to activate the IL-17 reporter with potencies ~0.1μM measured by EC50. These compounds were shown to directly bind to RORγ by Circular Dichroism-based thermal stability experiments. Furthermore, they can enhance an in vitro Th17 differentiation process in human primary T cells. As RORγremains an orphan nuclear receptor, discovery of these aryl amide compounds as functional agonists will now provide pharmacological tools for us to dissect functions of RORγ and facilitate drug discovery efforts for immune modulating therapies.

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