Molecular glues for protein-protein interactions: Progressing toward a new dream

The modulation of protein-protein interactions with small molecules is one of the most rapidly developing areas in drug discovery. In this review, we discuss advances over the past decade (2014-2023) focusing on molecular glues (MGs)-monovalent small molecules that induce proximity, either by stabilizing native interactions or by inducing neomorphic interactions. We include both serendipitous and rational discoveries and describe the different approaches that were used to identify them. We classify the compounds in three main categories: degradative MGs, non-degradative MGs or PPI stabilizers, and MGs that induce self-association. Diverse, illustrative examples with structural data are described in detail,…

• OP
  Ono Pharmaceutical
• OP
  Ono Pharma Foundation

  Award: GM147696
• NI
  National Institutes of Health

  Award: GM147696
• NI
  National Institute of General Medical Sciences

  Award: GM147696