A new series of non-peptidic, mono-acid protein tyrosine phosphatase 1B (PTP1B) inhibitors has been identified by structure-based design. Compounds with 2-(indol-3-yl)- and 2-phenyl-3,3,3-trifluoro-2-hydroxypropionic acid core units targeted at the enzyme's primary site and a hydrophobic chlorophenylthiazole extension in its 2° site exhibit 3-60 µM IC50s for PTP1B inhibition in an Sf9 cell-based assay. © 2007 Elsevier Ltd. All rights reserved.
- Insulin resistance
- Insulin sensitivity
- Protein tyrosine phosphatase 1B
- Structure-based design