Identification of ZINC02765569: a potent inhibitor of PTP1B by vHTS

The present study describes identification of a novel lead molecule ZINC02765569 for inhibition of protein tyrosine phosphatase 1B (PTP1B) enzyme by a high-throughput virtual screening of Zinc database against catalytic domain of PTP1B employing docking algorithm Glide. The identified hit molecule ZINC02765569 was synthesized and evaluated for in vitro PTP1B enzyme inhibition, in vitro cellular glucose uptake assay, and animal models of hyperglycemia. ZINC02765569 shows promising inhibition of PTP1B enzyme at 10 μm assay, positively up-regulate the cellular glucose uptake in skeletal cell muscle myotubes and SLM/STZ hyperglycemic animal experiments. The novel hit reported here should provide a platform for the further development of its analogs as potential PTP1B enzyme inhibitors.