Despite an increased investment in pharmaceutical research by industry and public funders, the productivity of drug development and the introduction of truly novel drugs have been in steady decline. The high failure rate at a late stage in clinical development is mostly due to limited understanding of the biology of the drug target and the disease. The impact of failures is compounded by the tendency of pharmaceutical research to focus on a small number of drug targets, leaving the majority of potential targets under-investigated and under-utilized.
The PITE-FAPESP was the public-private grant which established the SGC Chemical Biology Center at UNICAMP in 2015 (SGC-UNICAMP). Within the PITE grant our aim is to develop and provide chemical probes to the under-studied portion of the human kinome. This area was chosen because there is a vast expertise in developing kinase inhibitors, but most approved drugs and current drug development programs target a small subset (<10%) of kinases, mostly in oncology.
This project aims to deliver 8 chemical probes in collaboration with the other SGC centers and requires the combination of expertise from diverse areas, including medicinal chemistry, protein biochemistry, assay technology, crystallography and cell biology, as well as a network of external collaborators in clinical and other areas.
The project with Ache, which started in 2017 with 6-years duration, focuses on the development of inhibitors for cancer-related protein kinases. The Ache provides molecules made in house, which are sent to the CQMED/SGC to characterize the binding and activity on target proteins. Since the molecules bind to protein kinases, they are used to generate co-crystal structures with the target protein. The structural biology, obtained by X-ray diffraction data, allow us to understand the binding of the molecule to the protein. With this information, new chemical series are synthesized to improved binding, potency and selectivity. The project with Aché aims to generate sophisticated, highly selective and specific inhibitors. During 2018 potent molecules were developed, now we are focusing on the biochemical assays and medicinal chemistry to increase in the selectivity of the molecules.
The project with Eurofarma, also started in 2017 with 6-years duration, focuses of inhibitors for infectious diseases. The global SGC network and Eurofarma are providing target molecules and this partnership also involves DNDI (Drug for Neglected Disease Initiative). During 2018 the initial molecules were developed, and target proteins are being characterized.