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

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 activit...

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Veröffentlicht in:	Journal of medicinal chemistry 2008-08, Vol.51 (16), p.4948-4956
Hauptverfasser:	Lawrence, Harshani R, Pireddu, Roberta, Chen, Liwei, Luo, Yunting, Sung, Shen-Shu, Szymanski, Ann Marie, Yip, M. L. Richard, Guida, Wayne C, Sebti, Saïd M, Wu, Jie, Lawrence, Nicholas J
Format:	Artikel
Sprache:	eng
Schlagworte:	Antineoplastic agents Binding Sites Biological and medical sciences General aspects Indoles - chemical synthesis Indoles - pharmacology Inhibitory Concentration 50 Medical sciences Models, Molecular Pharmacology. Drug treatments Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors Protein Tyrosine Phosphatase, Non-Receptor Type 11 - antagonists & inhibitors Protein Tyrosine Phosphatase, Non-Receptor Type 6 - antagonists & inhibitors src Homology Domains - drug effects Sulfonic Acids - chemical synthesis Sulfonic Acids - pharmacology
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Zusammenfassung:	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.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm8002526