# An open degrader consortium against every undruggable driver transcription factor

Source: https://onco.cc/ideas/idea-moon-open-degrader-consortium/  
OnCo record `idea-moon-open-degrader-consortium` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Open pooling delivers clinical candidates against at least three undruggable drivers within six years, faster than any single closed programme has achieved for the same targets.
- Rationale: Pre-competitive sharing of probes and structures has repeatedly accelerated target validation; the largest risks in these targets are scientific, not commercial, so secrecy mainly buys duplication.
- Proposed test: Launch with three targets and five members; success is an open, validated in vivo-active degrader for at least one target within three years.
- Maturity: preclinical-evidence
- Actor: research

## Sources

- Open Targets: https://www.opentargets.org/

## 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/)
- targets: [KRAS](https://onco.cc/targets/kras/), [TP53](https://onco.cc/targets/tp53/)
- companies: [Arvinas](https://onco.cc/companies/arvinas/), [Kymera Therapeutics](https://onco.cc/companies/kymera/), [Monte Rosa Therapeutics](https://onco.cc/companies/monte-rosa/)
- bottlenecks: [Secrecy and intellectual property block collaboration](https://onco.cc/bottlenecks/b-ip-collaboration/), [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- key papers: [Vogelstein, Lane and Levine 2000: surfing the p53 network](https://onco.cc/key-papers/paper-vogelstein-surfing-p53-network-nature-2000/)

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