Centro de biologia quimica de proteinas quinases - alavancando desenvolvimento de farmacos atraves de pesquisa de acesso aberto.

Resumo

The > 500 protein kinases in the human genome are key regulators of virtually every physiological process. Kinases can be targeted by highly potent and selective small molecules. However, despite their importance and suitability for drug discovery, most academic and pharmaceutical research has focused on a small fraction of kinases; most kinases are under-explored. These under-explored kinases represent a rich source of new biology and are the focus of this proposal. The UNICAMP proposes to partner with the Structural Genomics Consortium (SGC) to focus on a target list of 26 under-explored kinases implicated in the regulation of RNA splicing and chromatin biology, and that linked to neurological diseases, angiogenesis, and cancer. From these kinases, SGC-UNICAMP aims to generate selective small molecule inhibitors (chemical probes) for at least 8. To accomplish this, we will establish a structure-guided medicinal chemistry platform (SGC-UNICAMP), with funding and advice from the SGC and its eight pharmaceutical partners and an external advisory board comprising leaders in chemical biology. The platform in collaboration with a network of academics in Campinas and around the world, will characterize the probes in biochemical assays to establish potency and selectivity, and in cellular assays to demonstrate on-target engagement in cells. Once the chemical probes meet stringent quality criteria, we will make them available to Brazilian and international scientists without restriction on use. The availability of these chemical probes will uncover new biological pathways and identify new opportunities for therapeutic intervention. By establishing the open access chemistry platform at UNICAMP, we hope to establish UNICAMP as one of the world center of kinase chemical biology. (AU)