Session: Posters:

Protein phosphatases have been considered a potential target for drug-based therapy since their discovery. Mutations of phosphatases found in cell signaling pathways have been linked to type II diabetes, obesity, and certain types of cancer. One of these phosphatases, protein tyrosine phosphatase 1B (PTP1B), functions as a negative regulator of the insulin pathway. A gene knockout study in mice confirmed that mutations to this protein result in a reduced insulin sensitivity. Previous attempts at active site-based inhibition through drug-based therapy have been unsuccessful, shifting the focus onto allosteric inhibitors. Potential allosteric sites were identified on PTP1B using the Graph-based Local Structure Alignment (G-LoSA) tool. In this study, compound 2-[(5Z)-5-benzylidene-4-oxo-2-thioxo-2,3-thiazolidin-3-yl]-N-pheylacetamide was synthesized and analyzed as an allosteric inhibitor of PTP1B. Enzymatic activity assays showed that the compound exhibited little inhibitory activity. Further exploration using x-ray crystallography could reveal key ligand-protein interactions.

Synthetic scheme of 2-[(5Z)-5-benzylidene-4-oxo-2-thioxo-2,3-thiazolidin-3-yl]-<i>N-</i>pheylacetamide

Synthetic scheme of 2-[(5Z)-5-benzylidene-4-oxo-2-thioxo-2,3-thiazolidin-3-yl]-N-pheylacetamide

Anne Reeve

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