An open degrader consortium against every undruggable driver transcription factor
Cancer's most important drivers, such as MYC and mutant p53, cannot be blocked with normal drugs. Pool effort and share results openly to build molecules that destroy them instead.
Targeted protein degradation (PROTACs, molecular glues) has produced clinical candidates for previously undruggable proteins, but efforts against the hardest targets are fragmented and duplicated under secrecy. Structural Genomics Consortium-style open science produced chemical probes for hundreds of proteins. The proposal is an open consortium with industry, academic and philanthropic members that generates and releases ligands, degraders, ternary complex structures and assays for the ten highest-value undruggable drivers (MYC, mutant TP53 variants, beta-catenin, KRAS G12D and rarer variants, fusion oncoproteins), with a pre-agreed rule that clinical candidates may be developed by any member.
- 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.