Identification of a benzo imidazole thiazole derivative as the specific irreversible inhibitor of protein tyrosine phosphatase

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• 作者：Lin Ge^a ; ^c ; ^&dagger ; ; Kang-shuai Li^a ; ^c ; ^&dagger ; ; Meng-meng Li^a ; Peng Xiao^a ; ^b ; Xu-ben Hou^b ; Xu Chen^c ; Hong-da Liu^a ; Amy Lin^d ; Xiao Yu^c ; Gui-jie Ren^a ; ^{rengj@sdu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Hao Fang^b ; ^{haofangcn@sdu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Jin-peng Sun^a ; ^{sunjinpeng@sdu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PTP ; STEP ; Covalent inhibitor ; Irreversible ; Probe
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 October 2016
• 年：2016
• 卷：26
• 期：19
• 页码：4795-4798
• 全文大小：1275 K

文摘

Protein tyrosine phosphatases (PTPs) play key roles in many physiological processes, including cell proliferation, differentiation, immune responses and neural activities. Inappropriate regulation of the PTP activity could lead to human diseases, such as cancer or diabetes. Functional studies of PTP can be greatly facilitated by chemical probes that covalently label the active site of a PTP through an activity-dependent chemical reaction. Here, we characterize compound E4 as a new class of PTP activity probes. Compound E4 inactivate STEP in a time- and concentration-dependent fashion. Further study showed that compound E4 inhibits a series of PTPs in a time dependent manner, whereas it shows little or no inhibition toward metal dependent protein phosphatases. Collectively, this new identified covalent inhibitor of PTPs has the potential to be developed to an active site Cys directed PTP probes to study the active properties of the PTPs in cell signaling.