Abstract
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 microM. 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.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Binding Sites
-
Indoles / chemical synthesis
-
Indoles / pharmacology*
-
Inhibitory Concentration 50
-
Models, Molecular
-
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
-
Sulfonic Acids / chemical synthesis
-
Sulfonic Acids / pharmacology*
-
src Homology Domains / drug effects
Substances
-
3-(2-(2-nitrophenyl)hydrazono)-2-oxoindoline-5-sulfonic acid
-
Indoles
-
Sulfonic Acids
-
Protein Tyrosine Phosphatase, Non-Receptor Type 1
-
Protein Tyrosine Phosphatase, Non-Receptor Type 11
-
Protein Tyrosine Phosphatase, Non-Receptor Type 6