Recent advance on PTP1B inhibitors and their biomedical applications

Since the year 2000, IDF has been measuring the prevalence of diabetes nationally, regionally and globally.

Prediction of small molecule binding modes to macromolecules of known three-dimensional structure is a problem of paramount importance in rational drug design (the "docking" problem). We report the development and validation of the program GOLD (Genetic Optimisation for Ligand Docking). GOLD is an automated ligand docking program that uses a genetic algorithm to explore the full range of ligand conformational flexibility with partial flexibility of the protein, and satisfies the fundamental requirement that the ligand must displace loosely bound water on binding. Numerous enhancements and modifications have been applied to the original technique resulting in a substantial increase in the reliability and the applicability of the algorithm. The advanced algorithm has been tested on a dataset of 100 complexes extracted from the Brookhaven Protein DataBank. When used to dock the ligand back into the binding site, GOLD achieved a 71% success rate in identifying the experimental binding mode.

New biological tools provide new techniques to probe fundamental biological processes. Here we describe the burgeoning field of Proteolysis Targeting Chimera (PROTACs) which are capable of modulating protein concentrations at a post-translational level by co-opting the Ubiquitin-Proteasome System. We describe the PROTAC technology, its application to drug discovery and provide examples where PROTACs have enabled novel biological insights. Furthermore, we provide a workflow for PROTAC development and use as well as a discussion of the benefits and issues associated with PROTACs. Finally, we compare PROTAC mediated protein level modulation with other technologies such as RNA interference and genome editing.