Identification of a benzo imidazole thiazole derivative as the specific irreversible inhibitor of protein tyrosine phosphatase. Issue 19 (1st October 2016)

• Record Type: Journal Article
• Authors: Ge, Lin; Li, Kang-shuai; Li, Meng-meng; Xiao, Peng; Hou, Xu-ben; Chen, Xu; Liu, Hong-da; Lin, Amy; Yu, Xiao; Ren, Gui-jie; Fang, Hao; Sun, Jin-peng
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 19(2016)
• Page Start: 4795
• Page End: 4798
• Publication Date: 2016-10-01
• Subjects: PTP -- STEP -- Covalent inhibitor -- Irreversible -- Probe; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.08.024
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 compoundE4 as a new class of PTP activity probes. CompoundE4 inactivate STEP in a time- and concentration-dependent fashion. Further study showed that compoundE4 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.