{"id":"W4407378559","doi":"10.1002/anie.202424373","title":"Binding‐Site Purification of Actives (B‐SPA) Enables Efficient Large‐Scale Progression of Fragment Hits by Combining Multi‐Step Array Synthesis With HT Crystallography","year":2025,"lang":"en","type":"article","venue":"Angewandte Chemie International Edition","topic":"Protein Degradation and Inhibitors","field":"Biochemistry, Genetics and Molecular Biology","cited_by":10,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Engineering and Physical Sciences Research Council; Fundação de Apoio à Pesquisa do Distrito Federal; Conselho Nacional de Desenvolvimento Científico e Tecnológico; Ontario Ministry of Economic Development and Innovation; Ministero dello Sviluppo Economico; International Seafood Sustainability Foundation; European Federation of Pharmaceutical Industries and Associations; Merck KGaA; Genome Canada; Fundação de Amparo à Pesquisa do Estado de São Paulo; Diamond Light Source; Novartis Pharma; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Pfizer","keywords":"Chemistry; Fragment (logic); Combinatorial chemistry; Ligand (biochemistry); Computer science; Ligand efficiency; Bromodomain; Target protein; Computational biology; Stereochemistry; Algorithm; Biochemistry; Biology","routes":{"ca_aff":false,"ca_fund":true,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":true},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0003776014,0.0005164972,0.0003203496,0.0003092283,0.0001522834,0.0003902676,0.0003776955,0.0002509974,0.002355597],"category_scores_gemma":[0.0002784456,0.0002276959,0.0003123019,0.0003086469,0.0002513593,0.0002950564,0.0004795732,0.000958075,0.001374699],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0003184565,"about_ca_system_score_gemma":0.0002852331,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0004282521,"about_ca_topic_score_gemma":0.0007965606,"domain_scores_codex":[0.9996889,0.00005271085,0.00002364397,0.00005700151,0.0001206414,0.00005719483],"domain_scores_gemma":[0.9998541,0.00003285451,0.00003324289,0.00003754415,0.00002034613,0.00002185714],"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":[0.00006491228,0.00006701601,0.0001105648,0.00005242323,0.000008168028,0.0000343741,0.0000182883,0.000614656,0.9926387,0.0002934204,0.0002053316,0.00589213],"study_design_scores_gemma":[0.00001683389,0.0002527598,0.0002958515,0.000003857965,0.000007445299,0.0000576141,0.000009503648,0.002348197,0.9941042,0.00008373973,0.002814676,0.000005260997],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.7943718,0.001243259,0.1939357,0.0003381322,0.00007098651,0.0004108823,0.001619688,0.001948025,0.00606155],"genre_scores_gemma":[0.8836876,0.000760306,0.1081477,0.0001072765,0.00001700662,0.0002644854,0.001535012,0.0002117423,0.005268887],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.002355597,"threshold_uncertainty_score":0.00788027,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.005609136689744027,"score_gpt":0.2476724685326363,"score_spread":0.2420633318428923,"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."}}