ideasIdea
Screen glue-like compounds against every cancer cell line and publish it
Some drugs work by sticking two proteins together so one destroys the other. These are usually found by luck. A large systematic search, published openly, would find many more.
Molecular glue degraders (thalidomide analogues, indisulam) were discovered serendipitously. Modern discovery pairs a chemical library with degradation readouts (global proteomics, reporter panels) across genetically diverse lines, using E3 ligase knockouts to confirm mechanism. A precompetitive atlas of compound-to-degraded-protein pairs would map which of the roughly 600 human E3 ligases can be redirected and against which classes of target.
Hypothesis
Systematic glue screening at scale identifies degradation of at least 50 proteins with no known small-molecule binding site, including at least five transcription factors of oncological interest.
Rationale
Glue mechanisms do not require a target pocket, so they extend the druggable proteome to interaction surfaces. The technology is now industrialised but siloed inside a handful of companies.
What would test it
A funded consortium screening 100,000 compounds with proteome-wide degradation readouts across 20 lines; success measured by independently confirmed novel degraded targets released publicly.
Maturity
preclinical evidence
Who has to act
philanthropy
Cost to try
Large (over $50M)
Years to first evidence
5
Bottlenecks it attacks
- The undruggable drivers · The proteins that drive most cancers, such as MYC, mutant p53 and most RAS variants, still have no good drug.
- Secrecy and intellectual property block collaboration · Companies with complementary drugs rarely test them together, and data that could answer questions stays locked up.