Potential Inhibitors of Protein Tyrosine Phosphatase (PTP1B) Enzyme: Promising Target for Type-II Diabetes Mellitus

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 on 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 decrease sensitivity of the insulin receptor is a pathological factor and also genetically linked problem causing type II diabetes.

Objectives: Insulin receptor sensitization is done by signal transduction mechanism via selective protein tyrosine phospha-tase (PTP1B). After interaction of insulin with its receptor, autophosphorylation of the intracellular part of the receptor takes place, turning it to an active kinase (sensitization). PTP1b is involved to the desensitization of the receptor by dephosphor-ylation. PTP1b inhibitors delay the receptor desensitization, prolonging insulin effect and making PTP1b 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-(benzyl-amino)-1-phenylethanol, urea, acetamides and piperazinylpropanols, phenylsulphonamides and phenylcarboxamide, ben-zamido, arylcarboxylic acid derivatives, arylsupfonyl derivatives, thiazoles, isothiozolidiones and thiazolodinones have been discussed citing the disease mechanisms.

Results: Therefore, 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.

Keywords: PTP1B inhibitors; TCPTP; Type-II diabetes mellitus; enzymes; insulin receptor.; protein tyrosine phosphatase 1B enzymes.