图 | Hervé Galons教授

题   目：Towards selective kinase inhibitors. Elucidation of their molecular mechanism of action

报告人：Hervé Galons

单   位：法国巴黎笛卡尔大学

时   间：2019年3月25日

地   点：上海大学量子与分子结构国际研究中心

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报告摘要

The development of precision medicine is giving a boost to the kinase drug discovery field. Not less than 7 kinase inhibitors were approved by the FDA in 2018, adding to the 4 which reached the market in 2017. Several of these drugs benefited from orphan drug designation. Cyclin dependent kinase (CDKs) have recently attracted interest as 3 CDK4/CDK6 inhibitors have been approved against estrogen positive breast cancer. Most of the recently marketed drugs are selective inhibitors. We wish to present our recent results in the discovery of potent inhibitors. Crystal structures and molecular modeling are guiding the design of new series of compounds. Their molecular targets were studied through affinity chromatography assays. The probes prepared for the identification of these molecular targets were also useful for a better understanding of the mechanism of diseases. These experiments guided us in the search of new inhibitors with distinct inhibition profiles. Among our most recently prepared families of inhibitors, selective inhibitors of CDK7 were identified following a kinome scan against 250 kinases. CDK7 control the activity of CDK2, CDK4, CDK6 and transcription. This kinase has been identified as a biomarker in several cancers. It can therefore be considered as a promising target for precision medicine. Unexpectedly, this series of compounds exhibited anti-angiogenic activity. Several of these compounds were even found more antiangiogenic than Sunitinib. The mechanism of the antiangiogenic activity is under investigation.

个人简介

Hervé Galons现任法国巴黎笛卡尔大学全职教授，其工作主要集中在两个领域：一是通过寻找能够纠正蛋白质错误折叠的化合物，开发神经退行性疾病的新疗法；二是发现并开发新激酶抑制剂。该项研究正在ManRos Therapeutics生物技术公司中进行，该由Hervé Galons与他人共同创办的公司同时也在对囊性纤维化中的细胞周期蛋白B激酶抑制剂进行II期临床研究。

会议简介

跨学科研究已成为现代科研的必然趋势，来自不同领域的专家携手合作，共同应对研究挑战，推动社会发展进步。以人类健康为例，这个主题涉及理解生物学基础知识，开发更佳的诊断和治疗方法等多个领域，也需要化学家们的通力合作。Elsevier爱思唯尔化学中国行活动，于2019年3月开展两场“化学促进健康”研讨会，分别在上海大学和清华大学举行，旨在与您一起探讨化学能为人类健康所做的贡献。本次研讨会将涵盖疾病调查、药物生产、健康监测等多个主题，邀请您及对该话题有兴趣的同事一同参与。

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