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Recent Advances in the Design and Synthesis of SH2 Inhibitors of Src, Grb2 and ZAP-70

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Abstract:

A perspective is offered on the recent development of Src-homology 2 (SH2) antagonists of Src, Grb2 and ZAP-70. Inhibiting Src SH2 is believed to be a potentially attractive way of regulating bone resorption. Grb2 SH2 has been shown to be an important component of the mitogenic ras pathway; and thus might be of utility in cancer research. ZAP-70 is a tyrosine kinase that is expressed solely in T-cells and natural killer cells. Since inhibition of the tandem SH2 domains of ZAP-70 has been shown to block T-cell proliferation, antagonists for this particular protein could have implications in immune suppression. The emphasis of the article is placed on the structure-based design, synthesis and biological activity of a number of newly reported SH2 antagonists in each of the three areas.

Keywords: Grb2; Grb2 SH2; Grb2 SH2 inhibitors; Immune suppression; Mitogenic ras pthway; Protein tyrosine kinases (PTKs); Protein tyrosine phosphatases (PTPs); SH2 inhibitors; Src; Src SH2 inhibitors; Src-homology 2 (SH2) antagonists; ZAP-70

Document Type: Review Article

DOI: https://doi.org/10.2174/0929867003374390

Publication date: 2000-10-01

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