{"entity":{"id":"molecular-glue-platforms","kind":"technology","name":"Molecular glue discovery platforms","aka":[],"tldr":"Molecular glues are small molecules that stick two proteins together so the cell destroys one of them. They are smaller and more drug-like than bifunctional degraders.","summary":"Thalidomide analogues work by gluing neosubstrates to cereblon; the field is now searching systematically for glues against chosen targets using chemoproteomics and machine learning. Monte Rosa, Nurix, C4 Therapeutics and Proxygen have clinical or near-clinical candidates against targets including cyclin K, GSPT1 and transcription factors. No purpose-designed molecular glue has been approved: the approved examples were discovered by accident decades ago.","status":"phase-1","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: molecular glue degrader","url":"https://clinicaltrials.gov/search?term=molecular%20glue%20degrader"}],"tags":["frontier","promising"],"related":["celmods"],"cancers":[],"sections":["drug-discovery","targeted-therapy"],"technologies":["protac-degrader","degrader-antibody-conjugate","ai-drug-design","crispr-screens"],"targets":[],"drugs":[],"companies":["monte-rosa","nurix","c4-therapeutics","kymera"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A small molecule remodels the surface of an E3 ligase so it recognises a protein it would normally ignore, marking that protein for proteasomal destruction.","strengths":["Oral, small and cell-permeable, unlike PROTACs","Reaches proteins with no active site","Catalytic: one molecule degrades many copies"],"limitations":["Discovery is still largely serendipitous","Cereblon-dependent glues fail where the ligase is absent or mutated","No approvals from rational design yet"]},"route":"/technologies/molecular-glue-platforms/","neighbours":{"technology":[{"id":"ai-drug-design","kind":"technology","name":"AI-driven drug & target discovery","route":"/technologies/ai-drug-design/"},{"id":"celmods","kind":"technology","name":"Cereblon E3 ligase modulators (CELMoDs)","route":"/technologies/celmods/"},{"id":"crispr-screens","kind":"technology","name":"CRISPR functional genomics","route":"/technologies/crispr-screens/"},{"id":"degrader-antibody-conjugate","kind":"technology","name":"Degrader-antibody conjugate (DAC)","route":"/technologies/degrader-antibody-conjugate/"},{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"}],"section":[{"id":"drug-discovery","kind":"section","name":"Drug Discovery Platforms","route":"/fronts/drug-discovery/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"company":[{"id":"c4-therapeutics","kind":"company","name":"C4 Therapeutics","route":"/companies/c4-therapeutics/"},{"id":"kymera","kind":"company","name":"Kymera Therapeutics","route":"/companies/kymera/"},{"id":"monte-rosa","kind":"company","name":"Monte Rosa Therapeutics","route":"/companies/monte-rosa/"},{"id":"nurix","kind":"company","name":"Nurix Therapeutics","route":"/companies/nurix/"}],"person":[{"id":"aaron-ciechanover","kind":"person","name":"Aaron Ciechanover","route":"/people/aaron-ciechanover/"}],"roadmap":[{"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":"frontier-2035","kind":"roadmap","name":"Radical oncology: what could change the war by 2035","route":"/roadmaps/frontier-2035/"},{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}],"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/"}],"term":[{"id":"imid","kind":"term","name":"Immunomodulatory drugs (IMiDs) and CELMoDs","route":"/terms/imid/"}],"pathway":[{"id":"ubiquitin-proteasome-system","kind":"pathway","name":"Ubiquitin-proteasome system & protein homeostasis","route":"/pathways/ubiquitin-proteasome-system/"}],"institution":[{"id":"technion","kind":"institution","name":"Technion, Israel Institute of Technology","route":"/institutions/technion/"}],"target":[{"id":"ikzf1","kind":"target","name":"IKZF1 (Ikaros)","route":"/targets/ikzf1/"},{"id":"ikzf3","kind":"target","name":"IKZF3 (Aiolos)","route":"/targets/ikzf3/"}]}}