DRUG REPURPOSING AS A SOURCE OF NOVEL MEDICATION FOR TYPE-2-DIABETES

Type 2 diabetes (T2D) is a major global health problem, with increasing costs associated with the therapeutic strategies. In the treatment of T2D, a number of drugs are used, including metformin and sulphonylureas. Despite of the fact that nearly 10% of the world's population is affected by the T2D, there are a limited number of therapeutic solutions. G-protein coupled receptors (GPCRs) represent the largest super-family of membrane receptors and a successful drug target. More than 30% of FDA-approved drugs target this class of receptors. Within the GPCR superfamily there is a family of receptors that mediates the biological effects of dietary fatty acids. It is called the free-fatty acid receptor family (abbreviated as FFAR) and is composed of four members: FFAR1, FFAR2, FFAR3 and FFAR4. Of these, FFAR1 and FFAR4 stimulate glucose-induced insulin secretion (GSIS), either directly, due to expression in beta-pancreatic cells (such as FFAR1) or indirectly by stimulating incretin production (FFAR4). These receptors are endogenously activated by dietary fatty acids from the omega-3 and omega-6 series and are considered emerging T2D therapeutic targets. With all the efforts of pharma companies, to date no new drugs, targeting FFAR1 or FFAR4, have been developed until the final approval stage. In this project, we propose the identification of specific agonists of FFAR1 and FFAR4 by functional analysis of the drugs already approved by the FDA, by a process called drug repositioning. The success of this project would have major therapeutic implications because the drugs already approved by the FDA have well-studied pharmacokinetic and pharmacodynamic characteristics, facilitating their use in the treatment of T2D.