Molecular glue discovery platforms
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.
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.
How it works
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.
- Oral, small and cell-permeable, unlike PROTACs
- Reaches proteins with no active site
- Catalytic: one molecule degrades many copies
- Discovery is still largely serendipitous
- Cereblon-dependent glues fail where the ligase is absent or mutated
- No approvals from rational design yet
Latest papers
topQuery for this technology: (TITLE:"Molecular glue discovery platforms" OR ABSTRACT:"Molecular glue discovery platforms") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Molecular glue discovery platforms, not a curated reading list.
Pages like this
not linked directly; found by shared links- TechnologyDe novo designed protein binders
Shares Radical oncology: what could change the war by 2035, AI-driven drug & target discovery and the tags frontier, promising.
- TechnologyLattice and GRID radiotherapy
Shares Radical oncology: what could change the war by 2035 and the tags frontier, promising.
- TechnologyRadiodynamic therapy and radiosensitising nanoparticles
Shares Radical oncology: what could change the war by 2035 and the tags frontier, promising.
- TechnologyChronotherapy: timing treatment to the body clock
Shares Radical oncology: what could change the war by 2035 and the tags frontier, promising.
- TechnologyEngineered exosomes as drug carriers
Shares Radical oncology: what could change the war by 2035 and the tags frontier, promising.
- TechnologyN-of-1 and rapid platform trials
Shares Radical oncology: what could change the war by 2035 and the tags frontier, promising.
- TechnologySelf-amplifying and circular RNA therapeutics
Shares Radical oncology: what could change the war by 2035 and the tags frontier, promising.
- TechnologySonodynamic therapy
Shares Radical oncology: what could change the war by 2035 and the tags frontier, promising.