As with thiazole-based compounds, isoxazole-based compounds also offered improvements over phenyl-based compounds. In general, modifications to this base scaffold similarly improved potency against PTPs, particularly with aromatic substitutions from the isoxazole ring. Notably, SHP1 showed a distinct preference for isoxazole-based compounds over analogous thiazole-based compounds when compared to other PTPs (Figure and Figure ). For example, benzothiazole 74 is preferred over benzisoxazole 39 for every PTP except for SHP1. Moreover, while compounds 37 and 73 perform essentially identically for most other PTPs, compound 37, the isoxazole, is a much more potent inhibitor of SHP1, and compound 36 is the most potent inhibitor of SHP1 (Figure ).