Novel protein tyrosine phosphatase 1B inhibitors: interaction requirements for improved intracellular efficacy in type 2 diabetes mellitus and obesity control

► PTP1B, an active player in insulin and leptin resistance. ► PTP1B chemical structure, substrates, activation/inactivation. ► The structural features of PTP1B molecule relevant to the interactions with inhibitors. ► The progress towards inhibitors with enhanced membrane permeability, affinity, specificity, and potency on intracellular PTP1B.