title: QSAR studies in the discovery of novel type-II diabetic therapies.
abstract: BACKGROUND
  Type-II diabetes mellitus (T2DM) is a complex chronic disease that represents a major therapeutic challenge. Despite extensive efforts in T2DM drug development, therapies remain unsatisfactory. Currently, there are many novel and important antidiabetic drug targets under investigation by many research groups worldwide. One of the main challenges to develop effective orally active hypoglycemic agents is off-target effects. Computational tools have impacted drug discovery at many levels. One of the earliest methods is quantitative structure-activity relationship (QSAR) studies. QSAR strategies help medicinal chemists understand the relationship between hypoglycemic activity and molecular properties. Hence, QSAR may hold promise in guiding the synthesis of specifically designed novel ligands that demonstrate high potency and target selectivity.
  
  
  METHODS
  This review aims to provide an overview of the QSAR strategies used to model antidiabetic agents. In particular, this review focuses on drug targets that raised recent scientific interest and/or led to successful antidiabetic agents in the market. Special emphasis has been made on studies that led to the identification of novel antidiabetic scaffolds.
  
  
  CONCLUSIONS
  Computer-aided molecular design and discovery techniques like QSAR have a great potential in designing leads against complex diseases such as T2DM. Combined with other in silico techniques, QSAR can provide more useful and rational insights to facilitate the discovery of novel compounds. However, since T2DM is a complex disease that includes several faulty biological targets, multi-target QSAR studies are recommended in the future to achieve efficient antidiabetic therapies.
authors.affiliation: a Department of Pharmaceutical Sciences, Faculty of Pharmacy , The University of Jordan , Amman 11942 , Jordan.
authors.forename: Areej
authors.initials: A
authors.lastname: Abuhammad
authors.affiliation: a Department of Pharmaceutical Sciences, Faculty of Pharmacy , The University of Jordan , Amman 11942 , Jordan.
authors.forename: Mutasem O
authors.initials: MO
authors.lastname: Taha
mesh_terms: D000818:Animals; D003198:Computer Simulation; D017076:Computer-Aided Design; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D021281:Quantitative Structure-Activity Relationship
chemical_list: D007004:Hypoglycemic Agents
keywords: DPP-IV; GSK-3β; PPAR; PTP-1B; QSAR; SGLT2; type 2 diabetes