{"entity":{"id":"degrader-antibody-conjugate","kind":"technology","name":"Degrader-antibody conjugate (DAC)","aka":[],"tldr":"An ADC that delivers a protein-destroying molecule instead of chemotherapy, hitting targets inside the cell that were previously unreachable.","summary":"A degrader-antibody conjugate is an ADC whose payload is a molecular glue or PROTAC rather than a cytotoxic: the antibody delivers it to the tumour cell and intracellular release triggers targeted protein degradation. Programmes include Orum Therapeutics (ORM-5029, a HER2-directed GSPT1 degrader; ORM-6151, CD33), Genentech (BRD4 degrader conjugates), and others. The design solves the delivery and bioavailability problems of PROTACs and lets a non-cytotoxic, non-genotoxic mechanism be targeted to the tumour, reaching intracellular targets via antibody selectivity. The trade-off is that potency per molecule is lower than for cytotoxics, and the field is early clinical, so it is not yet known whether degradation can match chemotherapy payloads in efficacy. The simple version is an ADC that destroys a specific protein inside the cancer cell instead of poisoning it.","status":"phase-1","asOf":"2026-09-04","links":[{"label":"The first PROTAC: a chimeric molecule that tags a protein for destruction (PNAS 2001)","url":"https://doi.org/10.1073/pnas.141230798"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["adcs","targeted-therapy"],"technologies":["adc","protac-degrader"],"targets":[],"drugs":[],"companies":["cullgen","firefly-bio","orum-therapeutics","prelude-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":["adc","protac-degrader"],"notes":[],"principle":"Antibody delivers a molecular glue or PROTAC payload; intracellular release triggers targeted degradation.","generation":"4th (next-gen)","strengths":["Non-genotoxic payload","Intracellular targets via antibody selectivity"],"limitations":["Potency per molecule lower than cytotoxics","Early stage"]},"route":"/technologies/degrader-antibody-conjugate/","neighbours":{"section":[{"id":"adcs","kind":"section","name":"Antibody-Drug Conjugates","route":"/fronts/adcs/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"antibody-oligonucleotide-conjugates","kind":"technology","name":"Antibody-oligonucleotide conjugates","route":"/technologies/antibody-oligonucleotide-conjugates/"},{"id":"molecular-glue-platforms","kind":"technology","name":"Molecular glue discovery platforms","route":"/technologies/molecular-glue-platforms/"},{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"}],"company":[{"id":"cullgen","kind":"company","name":"Cullgen","route":"/companies/cullgen/"},{"id":"firefly-bio","kind":"company","name":"Firefly Bio","route":"/companies/firefly-bio/"},{"id":"orum-therapeutics","kind":"company","name":"Orum Therapeutics","route":"/companies/orum-therapeutics/"},{"id":"prelude-therapeutics","kind":"company","name":"Prelude Therapeutics","route":"/companies/prelude-therapeutics/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"},{"id":"drug-discovery-roadmap","kind":"roadmap","name":"Drug discovery roadmap: screening in mice → maps of dependency → designing in silico","route":"/roadmaps/drug-discovery-roadmap/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}],"idea":[{"id":"idea-efflux-agnostic","kind":"idea","name":"Efflux-agnostic therapy for mesenchymal TNBC","route":"/ideas/idea-efflux-agnostic/"},{"id":"idea-bio1-antibody-degrader-conjugates","kind":"idea","name":"Use antibodies to deliver protein-destroying drugs into the right cells","route":"/ideas/idea-bio1-antibody-degrader-conjugates/"}],"paper":[{"id":"paper-protac-concept-sakamoto-pnas-2001","kind":"paper","name":"The first PROTAC: a chimeric molecule that tags a protein for destruction","route":"/key-papers/paper-protac-concept-sakamoto-pnas-2001/"}],"pathway":[{"id":"ubiquitin-proteasome-system","kind":"pathway","name":"Ubiquitin-proteasome system & protein homeostasis","route":"/pathways/ubiquitin-proteasome-system/"}]}}