{"entity":{"id":"idea-bio1-covalent-ligandability-atlas","kind":"idea","name":"An open map of which cancer proteins any drug can stick to","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The undruggable drivers): Dang et al., Drugging the 'undruggable' cancer targets (Nature Reviews Cancer 2017)","url":"https://doi.org/10.1038/nrc.2017.36"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["proteomics","ai-drug-design"],"targets":[],"drugs":[],"companies":["frontier-medicines"],"institutions":["broad-institute","icr-london"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-undruggable-targets","b-reproducibility"],"keyPapers":["paper-dang-nat-rev-cancer"],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"medium","horizonYears":4},"route":"/ideas/idea-bio1-covalent-ligandability-atlas/","neighbours":{"technology":[{"id":"ai-drug-design","kind":"technology","name":"AI-driven drug & target discovery","route":"/technologies/ai-drug-design/"},{"id":"proteomics","kind":"technology","name":"Proteomics & phosphoproteomics","route":"/technologies/proteomics/"}],"company":[{"id":"frontier-medicines","kind":"company","name":"Frontier Medicines","route":"/companies/frontier-medicines/"}],"institution":[{"id":"broad-institute","kind":"institution","name":"Broad Institute of MIT and Harvard","route":"/institutions/broad-institute/"},{"id":"icr-london","kind":"institution","name":"The Institute of Cancer Research","route":"/institutions/icr-london/"}],"bottleneck":[{"id":"b-reproducibility","kind":"bottleneck","name":"Preclinical results do not reproduce","route":"/bottlenecks/b-reproducibility/"},{"id":"b-undruggable-targets","kind":"bottleneck","name":"The undruggable drivers","route":"/bottlenecks/b-undruggable-targets/"}],"paper":[{"id":"paper-dang-nat-rev-cancer","kind":"paper","name":"Drugging the 'undruggable' cancer targets","route":"/key-papers/paper-dang-nat-rev-cancer/"}]}}