Navigating drug-targetome-phenotype interaction and their translational implications

抄録

Navigating the protein targets of drugs (hereafter, targetome) and deciphering the specific mechanisms of action at the molecular level of these interactions are critical steps in the development of drugs to treat human diseases. We have developed target protein identification methods including conventional affinity chromatography using labeled small molecules as well as recent methods using label-free small molecules such as Drug Affinity Responsive Target Stability (DARTS) and Cellular Thermal Shift Assay (CESTA) in combination with LC-MS/MS analysis to identify the targetome of drugs. The direct interaction between drug and the target protein is validated using biophysical, and bioinformatics tools. In addition, the biological relevance of this ‘drug-targetome-phenotype’ interaction is verified by genetic modulation, facilitating structure-based better drug design. In this presentation, our studies on target identification of ‘drug-targetome-phenotype’ interaction for navigating new mechanism of small molecules, target proteins, and their translational impact will be presented by introducing our case studies of protein target identification and validation of small molecules perturbing autophagy.