# Molecular glues that break the MYC-MAX partnership

Source: https://onco.cc/ideas/idea-bio1-myc-max-molecular-glue/  
OnCo record `idea-bio1-myc-max-molecular-glue` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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).

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017): https://doi.org/10.1038/nrc.2017.36

## Connected records

- technologies: [AI-driven drug & target discovery](https://onco.cc/technologies/ai-drug-design/), [PROTACs & molecular glues (targeted protein degradation)](https://onco.cc/technologies/protac-degrader/)
- companies: [C4 Therapeutics](https://onco.cc/companies/c4-therapeutics/), [Kymera Therapeutics](https://onco.cc/companies/kymera/), [Monte Rosa Therapeutics](https://onco.cc/companies/monte-rosa/)
- terms: [Oncogene addiction](https://onco.cc/terms/oncogene-addiction/)
- bottlenecks: [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- key papers: [Drugging the 'undruggable' cancer targets](https://onco.cc/key-papers/paper-dang-nat-rev-cancer/)

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