{"id":"W4414863170","doi":"10.1038/s41467-025-63928-8","title":"Discovery of a CNS active GSK3 degrader using orthogonally reactive linker screening","year":2025,"lang":"en","type":"article","venue":"Nature Communications","topic":"Protein Degradation and Inhibitors","field":"Biochemistry, Genetics and Molecular Biology","cited_by":17,"is_retracted":false,"has_abstract":true,"ca_institutions":"Discovery Centre","funders":"Biotechnology and Biological Sciences Research Council; Engineering and Physical Sciences Research Council; Research Councils UK; Diabetes UK; UK Research and Innovation; University of Dundee; Wellcome Trust; Medical Research Council; Directorate for Biological Sciences; Wellcome","keywords":"Drug discovery; Linker; In vivo; GSK-3; Druggability; Bifunctional; DNA ligase; Ubiquitin ligase","routes":{"ca_aff":true,"ca_fund":false,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0005876446,0.0004403747,0.0002926451,0.0002903371,0.0001262293,0.0004220007,0.0002041734,0.0003697673,0.0006902125],"category_scores_gemma":[0.000276455,0.0001454057,0.0002854981,0.0002469683,0.0002381654,0.000231455,0.0003236944,0.0003921087,0.0002603388],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0003511908,"about_ca_system_score_gemma":0.0003024666,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0002653302,"about_ca_topic_score_gemma":0.0005305394,"domain_scores_codex":[0.9997713,0.00004084254,0.00002090691,0.00004873462,0.00007530693,0.00004295912],"domain_scores_gemma":[0.9998364,0.00002793709,0.00006798442,0.00001601941,0.00002097088,0.0000306881],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"bench_or_experimental","study_design_gemma":"bench_or_experimental","study_design_scores_codex":[0.00007777769,0.00003556273,0.0001564624,0.00003588307,0.000007711654,0.0001071653,0.00001423107,0.000334635,0.9952808,0.0003338117,0.00005130639,0.003564619],"study_design_scores_gemma":[0.00001827512,0.0003299069,0.0002759668,0.000003637256,0.000009824171,0.0002064689,0.00000992817,0.0005994695,0.9967244,0.00005300614,0.001764439,0.000004569875],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9416267,0.001684426,0.05086863,0.0002382255,0.00003874302,0.0002717307,0.0007382166,0.000322859,0.004210466],"genre_scores_gemma":[0.9681277,0.001811384,0.0264424,0.0001213116,0.000007725606,0.00009316164,0.0007559087,0.00004596985,0.002594451],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.0006902125,"threshold_uncertainty_score":0.003107786,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.02207002199965231,"score_gpt":0.325207363743458,"score_spread":0.3031373417438057,"validation_status":"score_only:v0-immature-baseline","note":"Baseline scores from an immature model (maturity gate not passed). Scores rank; they never assert a category."}}