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Therapeutic Targeting of Protein Tyrosine Phosphatases for Novel Anti-Cancer Agents

日期: 2018-11-09
我院2018年度秋季学期学术系列讲座之十
题目:Therapeutic Targeting of Protein Tyrosine Phosphatases for Novel Anti-Cancer Agents 
讲座人:Zhong-Yin Zhang, PhD.
Distinguished Professor of Medicinal Chemistry, 
Robert C. and Charlotte P. Anderson Chair in Pharmacology, 
Head of the Department of Medicinal Chemistry and Molecular Pharmacology, 
Director of the Institute for Drug Discovery, 
Purdue University
时间:2018年11月9日(星期五),13:00-14:30
地点:我院邓祐才报告厅 
主持人:苏晓东教授
摘要:
Major insights into protein tyrosine phosphorylation mediated cellular events have been derived from studies of protein tyrosine kinases (PTKs) and it is common to view signaling pathways as cascades of reactions emanating from receptor tyrosine kinases. Understandably, drug discovery efforts to date have emphasized the PTKs. Given the reversible nature of protein tyrosine phosphorylation, it is not surprising that malfunction of protein tyrosine phosphatases (PTPs) is also known to be associated with a wide range of pathological conditions including cancer. Despite increasing interest in this important enzyme family, the function of most PTPs is still not well understood and the PTPs remain a largely under-exploited resource for therapeutic intervention. Among the contributing factors to the failure of targeting PTPs for drug discovery is the lack of detailed understanding of how dysregulation of PTP activity cause human diseases. In addition, the PTPs are exceptionally challenging targets for the development of potent and selective small molecule therapeutics due to the highly conserved and positively charged active sites. In this presentation, I describe our recent biochemical and genetic studies of oncogenic PTPs that yield new insights into the molecular basis that underlies the phosphatase-mediated tumorigenesis. I will also discuss several novel approaches for the acquisition of highly potent and selective PTP inhibitors with efficacious in vivo activity. Potent and specific PTP inhibitors could significantly facilitate functional analysis of the PTPs in complex cellular signal transduction pathways and may constitute valuable therapeutics for many human diseases.
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