Protein tyrosine phosphatase 1B (PTP1B) is an established target for diabetes and obesity but identifying drug-like PTP1B inhibitors has proved challenging. Haque et al. generated single-chain variable fragments of antibodies that stabilized the oxidized form of PTP1B and so inhibited its phosphatase function. Intracellular expression of the antibodies enhanced insulin-induced tyrosyl phosphorylation of the β-subunit of the insulin receptor and its substrate, and increased insulin-induced phosphorylation of AKT, suggesting that stabilization of the oxidized form of PTP1B could be a useful approach to design PTP inhibitors.
ORIGINAL RESEARCH PAPER
Haque, A. et al. Conformation-sensing antibodies stabilize the oxidized form of PTP1B and inhibit its phosphatase activity. Cell 147, 185–198 (2011)
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Harrison, C. A novel way of inhibiting a protein tyrosine phosphatase. Nat Rev Drug Discov 10, 902 (2011). https://doi.org/10.1038/nrd3618
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DOI: https://doi.org/10.1038/nrd3618
