In terms of overall fragment structure, our data revealed that aliphatic chloroacetamides were generally poor inhibitors of all PTPs tested, irrespective of their intrinsic reactivity (Figure ). Of the aryl chloroacetamides, thiazole-containing compounds, including those with relatively average intrinsic reactivity, showed significant phosphatase inhibition when compared to most other chemotypes (Figure and Figure ). This is particularly noteworthy, given recent reports of thiazole-derived sulfophenyl acetic amides as non-covalent inhibitors of the low molecular weight protein tyrosine phosphatase (LMW-PTP). Although the architecture of the LMW-PTP active site is distinct from that of classical PTPs, there are some structurally conserved features, including a catalytic loop and pTyr loop. We compared a crystal structure of LMW-PTP bound to a benzothiazole-containing non-covalent inhibitor with a covalent docking model of PTP1B bound to a benzothiazole-derived chloroacetamide (compound 74). Both proteins engage the benzothiazole in a similar orientation, suggesting that it may be a preferred scaffold for diverse tyrosine phosphatases (Figure ).