Developing a reliable computational method to determine the allosteric sites to be targeted in finding non-aggregating allosteric inhibitors of PTP1B

Type 2 diabetes is a serious metabolic disease with a growing need for improved therapeutics. Traditional antidiabetic drugs can assist with the maintenance of blood glucose levels in diabetics but are not optimal treatments due to side effects. PTP1B is a validated therapeutic target for type 2 diabetes, as it acts as a negative regulator in the insulin signaling pathway. Inhibiting PTP1B may allow for increased insulin sensitivity, leading to glucose homeostasis and improved metabolism. In the past 3 allosteric sites were identified as targets for PTP1B inhibition. This study analyzes the validity of these sites and the possibility of other allosteric sites through computational methods, organic synthesis, and enzymatic assays. A new allosteric site is identified and used to improve a computational method for testing possible inhibitors of PTP1B