PROteolysis TArgeting Chimeras (PROTACs) - Past, Present and Future

By M. Pettersson, C. Crews. Drug Discovery Today : Technologies, 2019

628 citations recorded by the source corpus.

The majority of currently used therapeutics are small molecule-based and utilize occupancy-driven pharmacology as the mode of action (MOA), in which the protein function is modulated via temporary inhibition. New modalities that operate using alternative MOAs are essential for tapping into the “undruggable” proteome. The PROteolysis Targeting Chimera (PROTAC) technology provides an attractive new approach that utilizes an event-driven MOA. Small molecule-based heterobifunctional PROTACs modulate protein target levels by hijacking the ubiquitin-proteasome system to induce degradation of the target. Here, we address important milestones in the development of the PROTAC technology, as well as emphasize key findings from this previous year and highlight future directions of this promising drug discovery modality.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/8c620abd2faddc6c112c79f2ef12553a833ac79d

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Citations in the corpus

• Modeling the CRL4A ligase complex to predict target protein ubiquitination induced by cereblon-recruiting PROTACs (2022, background): “2 B ); (2) “ open CRL4A ligase complexes, ” with a greater distance ( > 4 Å) between CRBN and E2 (conformations 3, 10, 11, and 12; Fig.”