# Molecular glue discovery platforms

Source: https://onco.cc/technologies/molecular-glue-platforms/  
OnCo record `molecular-glue-platforms` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Technology
- Status: phase-1
- Last checked: 2026-09-08
- Tags: frontier; promising
- 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

## Sources

- ClinicalTrials.gov: molecular glue degrader: https://clinicaltrials.gov/search?term=molecular%20glue%20degrader

## Connected records

- technologies: [AI-driven drug & target discovery](https://onco.cc/technologies/ai-drug-design/), [Cereblon E3 ligase modulators (CELMoDs)](https://onco.cc/technologies/celmods/), [CRISPR functional genomics](https://onco.cc/technologies/crispr-screens/), [Degrader-antibody conjugate (DAC)](https://onco.cc/technologies/degrader-antibody-conjugate/), [PROTACs & molecular glues (targeted protein degradation)](https://onco.cc/technologies/protac-degrader/)
- fronts: [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- 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/), [Nurix Therapeutics](https://onco.cc/companies/nurix/)
- people: [Aaron Ciechanover](https://onco.cc/people/aaron-ciechanover/)
- roadmaps: [Drug discovery roadmap: screening in mice → maps of dependency → designing in silico](https://onco.cc/roadmaps/drug-discovery-roadmap/), [Radical oncology: what could change the war by 2035](https://onco.cc/roadmaps/frontier-2035/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)
- key papers: [The first PROTAC: a chimeric molecule that tags a protein for destruction](https://onco.cc/key-papers/paper-protac-concept-sakamoto-pnas-2001/)
- terms: [Immunomodulatory drugs (IMiDs) and CELMoDs](https://onco.cc/terms/imid/)
- pathways: [Ubiquitin-proteasome system & protein homeostasis](https://onco.cc/pathways/ubiquitin-proteasome-system/)
- institutions: [Technion, Israel Institute of Technology](https://onco.cc/institutions/technion/)
- targets: [IKZF1 (Ikaros)](https://onco.cc/targets/ikzf1/), [IKZF3 (Aiolos)](https://onco.cc/targets/ikzf3/)

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