Inhibitors of Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (Shp2) Based on Oxindole Scaffolds

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• 作者：Harshani R. Lawrence ; Roberta Pireddu ; Liwei Chen ; Yunting Luo ; Shen-Shu Sung ; Ann Marie Szymanski ; M. L. Richard Yip ; Wayne C. Guida ; Saï ; d M. Sebti ; Jie Wu ; Nicholas J. Lawrence
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：August 28, 2008
• 年：2008
• 卷：51
• 期：16
• 页码：4948-4956
• 全文大小：225K
• 年卷期：v.51,no.16(August 28, 2008)
• ISSN：1520-4804

文摘

Screening of the NCI diversity set of compounds has led to the identification of 5 (NSC-117199), which inhibits the protein tyrosine phosphatase (PTP) Shp2 with an IC₅₀ of 47 μM. A focused library incorporating an isatin scaffold was designed and evaluated for inhibition of Shp2 and Shp1 PTP activities. Several compounds were identified that selectively inhibit Shp2 over Shp1 and PTP1B with low to submicromolar activity. A model for the binding of the active compounds is proposed.