QSAR Studies of PTP1B Inhibitors: Recent Advances and Perspectives

F.      Luan; X.      Xu; H.T.      Liu; M.N.D.S.      Cordeiro; X.Y.      Zhang

doi:10.2174/092986712802884196

Abstract

Diabetes mellitus, a chronic condition caused by defects in insulin secretion, or action, or both, is a group of metabolic disorders, complications of which can contribute significantly to ill health, disability, poor quality of life and premature death. From the three main types of diabetes, Type 2 is by far the most common, accounting for about 90% of cases worldwide. Studies on the role of protein tyrosine phosphatase 1B (PTP1B) have clearly shown that it serves as a key negative regulator of insulin signaling and is involved in the insulin resistance associated with Type 2 diabetes. The present work aims to survey information related to PTP1B research published in the last decade. Emphasis is laid particularly on Quantitative Structure-Activity Relationships (QSAR) based studies that supported so far the design of new, potent and selective PTP1B inhibitors. Finally, the challenges and perspectives of QSAR studies in this field are discussed to show how these method can be used to design new chemical entities with enhanced PTP1B inhibition activity.

Keywords: Diabetes mellitus, protein tyrosine phosphatase 1B inhibitors, type 2 diabetes, drug design, virtual screening, quantitative structure-activity relationships (QSAR), 3D-QSAR, comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), 2D-QSAR, multiple linear regression (MLR), radial basis function neural networks (RBFNN)