Chapter 3: The Challenge of Prosecuting Intracellular Protein–Protein Interactions: A Multi-modality Examination of Chemical Matter Identification, Biophysical Characterization, and Membrane Permeability

This review focuses on some of the latest approaches to developing small molecule, peptide, and antibody therapeutics as inhibitors of intracellular protein–protein interactions (PPIs). While distinct, each class of therapeutics relies on identifying chemical matter, accurately characterizing the interaction, optimizing the molecule for permeability, and engineering drug-like properties into the modality. It is undoubtedly an optimistic time as tremendous developments have been made across each of these areas in the last decade. This review will detail the advantages and disadvantages of these therapeutic modalities with a focus on recent advances as they relate to ligand ability and permeability.