Background:
There has been growing interest in the development of highly potent and
selective protein tyrosine phosphatase (PTP1B) inhibitors for the past 2-3 decades. Though most
PTPs share a common active site motif, the interest in selective inhibitors, particularly against PTP1B
is increasing to discover new chemical entities as antidiabetic agents. In the current paradigm to find
potent and selective PTP1B inhibitors, which is currently considered as one of the best validated
biological targets for non-insulin-dependent diabetic and obese individuals, resistance to insulin due
to decreased sensitivity of the insulin receptor is a pathological factor and is also genetically linked,
causing type II diabetes.
Objectives:
Insulin receptor sensitization is performed by a signal transduction mechanism via a
selective protein tyrosine phosphatase (PTP1B). After the interaction of insulin with its receptor,
autophosphorylation of the intracellular part of the receptor takes place, turning it into an active
kinase (sensitization). PTP1B is involved in the desensitization of the receptor by dephosphorylation.
PTP1b inhibitors delay the receptor desensitization, prolonging insulin effect and making PTP1B as a
drug target for the treatment of diabetes II. Therefore, it has become a major target for the discovery
of potent drugs for the treatment of type II diabetes and obesity. An attempt has been made in the
present study to discuss the latest design and discovery of protein tyrosine phosphatase (PTP1B) inhibitors.
Methods:
Many PTP1B inhibitors such as diaminopyrroloquinazoline, triazines, pyrimido triazine derivatives,
2-(benzylamino)-1-phenylethanol, urea, acetamides and piperazinylpropanols,
phenylsulphonamides and phenylcarboxamide, benzamido, arylcarboxylic acid derivatives, arylsupfonyl
derivatives, thiazoles, isothiozolidiones and thiazolodinones have been discussed, citing the disease
mechanisms.
Results:
The reader will gain an overview of the structure and biological activity of recently developed
PTPs inhibitors.
Conclusion:
The co-crystallized ligands and the screened inhibitors could be used as a template for
the further design of potent congeners.
Computational Insight into Protein Tyrosine Phosphatase 1B Inhibition: A Case Study of the Combined Ligand- and Structure-Based Approach
