# An open map of which cancer proteins any drug can stick to

Source: https://onco.cc/ideas/idea-bio1-covalent-ligandability-atlas/  
OnCo record `idea-bio1-covalent-ligandability-atlas` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Most cancer proteins have never been tested to see whether a small molecule can attach to them at all. A public map of what is chemically reachable would tell the field where to aim.

## Summary

Activity-based protein profiling with covalent fragment libraries can measure ligandable sites across thousands of proteins in cancer cell lysates and live cells. Existing datasets are partial and largely proprietary. A precompetitive atlas covering the cysteine, lysine and tyrosine proteomes across 50 cancer models, published openly with hit compounds deposited, would convert 'undruggable' from an assertion into a measurement.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Systematic covalent fragment profiling identifies ligandable sites on at least 200 proteins currently classified as undruggable, and at least ten of these yield functional chemical probes within three years.
- Rationale: The approach found the ligandable site that became the KRAS G12C drug class. Coverage, not concept, is the limiting factor, and the cost per protein falls sharply with shared infrastructure.
- Proposed test: Fund two chemoproteomics centres for three years with mandated quarterly public data release; count new ligandable sites and probes independently reproduced by a third laboratory.
- Maturity: preclinical-evidence
- Actor: philanthropy

## Sources

- Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017): https://doi.org/10.1038/nrc.2017.36

## Connected records

- technologies: [AI-driven drug & target discovery](https://onco.cc/technologies/ai-drug-design/), [Proteomics & phosphoproteomics](https://onco.cc/technologies/proteomics/)
- companies: [Frontier Medicines](https://onco.cc/companies/frontier-medicines/)
- institutions: [Broad Institute of MIT and Harvard](https://onco.cc/institutions/broad-institute/), [The Institute of Cancer Research](https://onco.cc/institutions/icr-london/)
- bottlenecks: [Preclinical results do not reproduce](https://onco.cc/bottlenecks/b-reproducibility/), [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- key papers: [Drugging the 'undruggable' cancer targets](https://onco.cc/key-papers/paper-dang-nat-rev-cancer/)

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