Fragment-based drug discovery (FBDD) is a strategy that has emerged in recent years as an additional and contrasting approach to other drug discovery strategies. This approach involves constructing fragments, small molecules with low molecular weight, which are potent ligands for a specific target. Currently, a class of receptors known as Activated Receptors peroxisome proliferators (PPAR) has aroused the interest of pharmaceutical industries due to its relation with lipid metabolism regulation. Considering that PPARs are promising targets for drug discovery, this project proposes the development of a compound library by fragment-based drug discovery, applying fragment merging and fragment growing. Regarding fragment merging, novel compounds will be obtained from the substitution of the bicyclic core of know PPAR agonists by selected fragments, 2,6-naphthyridin-3-ol and 1H-pyrazolo[3,4-c]pyridin-5-ol. The fragment growing approach aims at fragment elaboration to explore new receptor/ligand interactions. Concomitantly to the synthetic process, the library will be target to virtual screening - Docking - as well as biochemical assays - FRET - in order to evaluate the ligand efficiency of these novel fragments. Obtained data will be used to continue the fragment elaboration cycle, as well as tp better understand the PPAR receptors.
News published in Agência FAPESP Newsletter about the scholarship: