illustrates the relative portion of classes of chemical compounds utilized in the TPDs-related research. The area is strongly dominated by small molecules, followed by biosequences, including peptides, proteins, and nucleic acids. Indeed, the early protein-targeting chimeric molecules were peptide-based , with the first invention and design of a small molecule androgen receptor degrader using nutlin-3 for recruiting of MDM2 published in 2008 . The roles of these substances in the protein degraders-related research The motivation to explore the TPD strategy to attack diseases has been the existence of a large group of undruggable disease-causing proteins which can be considered potential targets for the degraders. The variety of diseases aimed by protein degraders as revealed by our analysis of the publications in the CAS Content Collection are shown in Figure . The largest portion (44%) of the publications are associated with cancer treatment, with neurodegenerative, infectious, and inflammatory diseases also highly represented (Figure ). CRBN, VHL, and MDM2 are the most popular E3 ligases being recruited by TPDs to induce ubiquitination and subsequent proteasomal degradation of a target proteins (Figure ). Collection for the three most widely used E3 ligases with the targeted diseases (percentages are from the total number of protein degraders-related publications).