Cambridge Healthtech Institute’s 17th Annual
Small Molecule Lead Discovery and Optimization for Difficult Drug Targets
APRIL 3 - 4, 2024
Cambridge Healthtech Institute's Protein-Protein Interactions (PPIs) conference covers discovery or design, and optimization of compounds that either disrupt or stabilize protein-protein or protein-nucleic acid complexes that cause disease. These complexes are also often intracellular and therefore only amenable to cell-penetrating compounds such as small molecules and newer modalities like (macro)cyclic peptides. However, they have been typically considered ‘difficult-to-drug' because their flat interaction surfaces make the PPIs harder for small molecules to gain a foothold. Furthermore, they are not typically enzymes, so traditional high-throughput enzymatic assay-based screening for identifying small molecule drug leads hasn't been possible. Recent advances that have spurred progress include: biophysical techniques that screen for molecular interactions rather than an enzymatic event, covalent drug discovery strategies, fragment-based ligand approaches, and structure-based drug design. Induced proximity and targeted protein degradation (TPD) 'destroy what you can't inhibit' approaches have also furthered the field and will be covered tangentially. Join fellow medicinal, biophysical, and structural chemists to learn the latest, share insights, and discuss strategies.