{"id":"W4407710920","doi":"10.26434/chemrxiv-2025-hn2j6","title":"Structure-guided design of ISOX-DUAL-based Degraders targeting BRD4 and CBP/EP300. A case of Degrader collapse","year":2025,"lang":"en","type":"preprint","venue":"ChemRxiv","topic":"Semiconductor materials and devices","field":"Engineering","cited_by":1,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Blood Cancer UK; Ontario Genomics Institute; European Federation of Pharmaceutical Industries and Associations; Merck KGaA; Ontario Genomics; Genome Canada; McGill University; Bayer; Genentech; Deutsche Krebshilfe; Pfizer; Deutsche Forschungsgemeinschaft; Engineering and Physical Sciences Research Council; Bristol-Myers Squibb","keywords":"Dual (grammatical number); Computer science","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":"codex-gemma-dda1882f352a","candidate_categories":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.000244436,0.0004426709,0.0008416325,0.0002190071,0.00003966186,0.0000484856,0.0001973326,0.0004506554,0.0001095256],"category_scores_gemma":[0.0001321945,0.0004375829,0.0001132914,0.0001920992,0.0001222398,0.00005019267,0.0001479834,0.000282882,5.530769e-7],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00005395762,"about_ca_system_score_gemma":0.0001555255,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0002618509,"about_ca_topic_score_gemma":0.00001605533,"domain_scores_codex":[0.9983323,0.00006899214,0.0007414798,0.0004131542,0.0001553847,0.0002886771],"domain_scores_gemma":[0.9988142,0.0002216799,0.0002696282,0.0004596439,0.000142142,0.00009268441],"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":[0.00003517426,0.00002995937,0.0004844064,0.007568703,0.0003194761,0.0001086148,0.0007809233,0.06053199,0.9269655,0.00005113145,0.002968559,0.0001555337],"study_design_scores_gemma":[0.0006378214,0.00001947343,0.00007612822,0.0005097073,0.0001893296,0.00004949687,0.0003122009,0.01839851,0.9789091,0.0003899455,0.00007109105,0.0004371271],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9924794,0.004272539,0.001558533,0.00002227625,0.0007472237,0.0005027787,0.0001208955,0.0001496423,0.0001467455],"genre_scores_gemma":[0.9862531,0.0001059125,0.01335895,0.00003473335,0.00008321079,0.00002935107,0.00005767841,0.00005317969,0.00002392624],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.05194363,"threshold_uncertainty_score":0.9998076,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.03418237898666966,"score_gpt":0.2590706167007647,"score_spread":0.2248882377140951,"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."}}