{"entity":{"id":"paper-bekes-nat-rev-drug-discov","kind":"paper","name":"PROTAC targeted protein degraders: the past is prologue","aka":[],"tldr":"Paper cited by one pathway page, indexed on Europe PMC as PubMed record 35042991 and published in Nature Reviews Drug Discovery; the citing page links this DOI, which is how the record was matched.","summary":"Targeted protein degradation (TPD) is an emerging therapeutic modality with the potential to tackle disease-causing proteins that have historically been highly challenging to target with conventional small molecules. In the 20 years since the concept of a proteolysis-targeting chimera (PROTAC) molecule harnessing the ubiquitin-proteasome system to degrade a target protein was reported, TPD has moved from academia to industry, where numerous companies have disclosed programmes in preclinical and early clinical development. With clinical proof-of-concept for PROTAC molecules against two well-established cancer targets provided in 2020, the field is poised to pursue targets that were previously considered 'undruggable'. In this Review, we summarize the first two decades of PROTAC discovery and assess the current landscape, with a focus on industry activity. We then discuss key areas for the future of TPD, including establishing the target classes for which TPD is most suitable, expanding the use of ubiquitin ligases to enable precision medicine and extending the modality beyond oncology.\n\nIndexed on Europe PMC as PubMed record 35042991 (DOI 10.1038/s41573-021-00371-6). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Rev Drug Discov 2022","url":"https://doi.org/10.1038/s41573-021-00371-6"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35042991/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35042991"}],"tags":["europepmc-ingest"],"related":["ubiquitin-proteasome-system"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-reviews-drug-discovery"],"dependsOn":[],"notes":[],"journal":"Nature Reviews Drug Discovery","year":2022,"doi":"10.1038/s41573-021-00371-6","pmid":"35042991","authors":"Békés M, Langley DR, Crews CM","paperType":"review","findings":[],"whatItMeans":"One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-bekes-nat-rev-drug-discov/","neighbours":{"pathway":[{"id":"ubiquitin-proteasome-system","kind":"pathway","name":"Ubiquitin-proteasome system & protein homeostasis","route":"/pathways/ubiquitin-proteasome-system/"}],"journal":[{"id":"nature-reviews-drug-discovery","kind":"journal","name":"Nature Reviews Drug Discovery","route":"/journals/nature-reviews-drug-discovery/"}]}}