{"entity":{"id":"idea-bio1-myc-max-molecular-glue","kind":"idea","name":"Molecular glues that break the MYC-MAX partnership","aka":[],"tldr":"MYC is a cancer-driving transcription factor with no drug because it has no binding pocket. A molecular glue or degrader that jams its required partner MAX, or recruits an E3 ligase to the MYC-MAX interface, could switch it off; gluing disordered proteins now has precedent from cereblon-binding drugs.","summary":"MYC must dimerise with MAX to bind DNA. Rather than seeking an inhibitor pocket on MYC, a molecular glue or bifunctional degrader could stabilise a non-productive MYC conformation or recruit an E3 ligase to the MYC-MAX interface. Precedent for gluing intrinsically disordered proteins now exists (for example the recruitment of transcription factors to cereblon by aryl sulfonamides and CELMoD-class agents).","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["protac-degrader","ai-drug-design"],"targets":[],"drugs":[],"companies":["monte-rosa","c4-therapeutics","kymera"],"institutions":[],"pathways":[],"terms":["oncogene-addiction"],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A compound that reduces nuclear MYC protein by 80 percent for 24 hours produces tumour regression in MYC-amplified xenografts with tolerable effects on regenerating tissues.","rationale":"Degradation avoids the need for a binding pocket, which is why glues have already drugged the previously intractable IKZF1/3 and RBM39. MYC has a short half-life, so partial degradation should have a large functional effect.","test":"Chemoproteomic glue screening against MYC-MAX in a MYC-amplified line with degradation readout, followed by tolerability studies in mouse models where MYC is required for gut and marrow renewal.","maturity":"preclinical-evidence","actor":"industry","cost":"large","horizonYears":8},"route":"/ideas/idea-bio1-myc-max-molecular-glue/","neighbours":{"technology":[{"id":"ai-drug-design","kind":"technology","name":"AI-driven drug & target discovery","route":"/technologies/ai-drug-design/"},{"id":"protac-degrader","kind":"technology","name":"PROTACs & molecular glues (targeted protein degradation)","route":"/technologies/protac-degrader/"}],"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/"}],"term":[{"id":"oncogene-addiction","kind":"term","name":"Oncogene addiction","route":"/terms/oncogene-addiction/"}],"bottleneck":[{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"paper":[{"id":"paper-dang-nat-rev-cancer","kind":"paper","name":"Drugging the 'undruggable' cancer targets","route":"/key-papers/paper-dang-nat-rev-cancer/"}]}}