Background: Protein tyrosine phosphatase 1B (PTP1B) is an important therapeutic target
for type II diabetes and obesity because of its pivotal role as a negative modulator in both insulin and
leptin signalling pathways.
Objective: The discovery of PTP1B inhibitors has been the focus of researchers in both academia and
pharmaceutical industry over the last two decades.
Results and Conclusion: Though, intense pharmaceutical research in this area has resulted in many potent
PTP1B inhibitors, a vast majority of them possessed pTyr mimetic group such as phosphonates, carboxylic
acids and sulphamic acids, which led to poor PTP1B selectivity and insufficient in vivo efficacy
due to low cell permeability and bioavailability. The availability of X-ray crystallographic structures of
PTP1B together with the application of molecular modelling and other innovative strategies led to the
development of many potent and selective PTP1B inhibitors with desirable physicochemical properties.
This review traces the development of PTP1B inhibitors over the last decade and also records novel
PTP1B inhibitors developed recently with greater emphasis on their selectivity and cell permeability.