{"entity":{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","aka":[],"tldr":"Instead of blocking a protein, these drugs tag it for the cell's own garbage disposal, removing it entirely.","summary":"Vepdegestrant (Veppanu, Arvinas/Pfizer), an oral ER PROTAC, became the first approved PROTAC in 2026 for ESR1-mutant HR+ breast cancer (VERITAC-2). Molecular glues (lenalidomide, pomalidomide, and next-generation CELMoDs iberdomide, mezigdomide) are established in myeloma. Degraders of AR, BTK, BCL6, KRAS, IKZF1/3, and the 'undruggable' transcription factors are in the clinic. Degrader-antibody conjugates deliver them selectively.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Proteolysis_targeting_chimera","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Proteolysis_targeting_chimera"}],"tags":[],"related":["idea-senolytics-after-chemo","stablix"],"cancers":[],"sections":["targeted-therapy"],"technologies":["degrader-antibody-conjugate"],"targets":["estrogen-receptor","androgen-receptor","kras"],"drugs":["vepdegestrant"],"companies":["arvinas","pfizer","bms","amphista-therapeutics","boundless-bio","captor-therapeutics","cullgen","firefly-bio","foghorn-therapeutics","neomorph","orum-therapeutics","photys-therapeutics","plexium","prelude-therapeutics","proxygen","treeline-biosciences","triana-biomedicines"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Bifunctional molecule recruits an E3 ubiquitin ligase (cereblon, VHL) to the target, causing ubiquitination and proteasomal destruction.","strengths":["Event-driven (catalytic), removes scaffolding functions","Reaches non-enzymatic targets"],"limitations":["Large molecules with poor oral bioavailability (PROTACs)","Hook effect","E3 ligase expression varies"],"since":2026},"route":"/technologies/protac-degrader/","neighbours":{"idea":[{"id":"idea-moon-open-degrader-consortium","kind":"idea","name":"An open degrader consortium against every undruggable driver transcription factor","route":"/ideas/idea-moon-open-degrader-consortium/"},{"id":"idea-fund-precompetitive-undruggable-consortium","kind":"idea","name":"An open-science consortium on the undruggable drivers, open until a candidate","route":"/ideas/idea-fund-precompetitive-undruggable-consortium/"},{"id":"idea-bio1-paralog-synthetic-lethality","kind":"idea","name":"Attack the backup copy when a tumour has lost the original 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