Activity: Publication peer-review and editorial work types › Editorial activity
Dear Colleagues, It is indisputable that there is a need to expand the druggable genome since only a small portion of it is pharmaceutically accessible to classical drug discovery approaches. Transcription factors, scaffolding proteins, pharmacological chaperones and multi-subunit enzymes have in major part been considered no go targets. These target classes rarely present deep active sites that can bind small molecules with high affinity, and in contrast function via formation of specific protein–protein interactions (PPIs). These interactions are considered difficult, due to the often large and flat surface areas that need to be targeted. Ligandability challenges, combined with historic failures of early high-throughput screening campaigns by the pharmaceutical industry against PPI targets, rapidly contributed to perceiving PPIs as “undruggable” space. In recent years, however, these perceptions and misconceptions about targeting protein–protein interactions are beginning to break. Dozens of drug-like small molecules and peptides that target different protein-protein interactions have entered clinical trials or even they are approved (e.g., tirofiban, Merck). Many chemical probes that intervene onto specific PPIs have been developed by industry and academia, opening tremendous new opportunities to explore biology. Targeting protein-protein interaction is, nowadays, a highly rewarding scientific endeavour, providing many opportunities to modalities of chemical intervention other than conventional inhibition, and beyond traditional Rule-of-5 compliant chemical space. Researchers in the field of chemical biology and drug discovery of protein-protein interactions are cordially invited to contribute with original papers and reviews to this Special Issue of Molecules, which report on the design and synthesis, evaluation and development of new small molecules or peptides that target to protein–protein interactions or new computational and biophysical approaches and technologies to target protein–protein interactions. Prof. Dr. Alessio Ciulli Dr. Carles Galdeano Guest Editors