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.
- insulin resistance
- insulin sensitivity
- protein tyrosine phosphatase 1B
- structure-based design