Ligand Based Screening Tools for Insulin Receptor Activating Compounds

Current treatments of type 2 diabetes mellitus have sometimes severe side effects. Therefore, the identification of new treatments is still an urgent need. The binding of insulin to the extracellular part of the insulin receptor is a key step in the insulin signalling pathway. As type 2 diabetes is characterized among others by a resistance of cells against insulin, activating the insulin receptor might be an interesting approach. In 1999, Zhang et al. discovered a small molecule from a fungal extract which activates the human insulin receptor by binding directly to its intracellular domain [1]. This compound (L-783,281 or demethylasterriquinone B-1, DMAQ-B1) was shown to lower blood glucose levels in mouse models of type 2 diabetes mellitus.