{"id":"W4405107102","doi":"10.1021/acs.jmedchem.4c01995","title":"Structure-Based Discovery of a Series of Covalent, Orally Bioavailable, and Selective BFL1 Inhibitors","year":2024,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Cell death mechanisms and regulation","field":"Biochemistry, Genetics and Molecular Biology","cited_by":3,"is_retracted":false,"has_abstract":true,"ca_institutions":"Discovery Centre","funders":"","keywords":"Chemistry; In vivo; Covalent bond; Lead compound; Enzyme; Structure–activity relationship; Programmed cell death; Caspase; In vitro; Bioavailability; Computational biology; Biochemistry; Apoptosis; Pharmacology; Genetics; Biology","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":[0.0001513145,0.0005125175,0.0002936062,0.0003788004,0.0001564293,0.0003009137,0.0003331133,0.0002499648,0.001508076],"category_scores_gemma":[0.0001292918,0.0001703049,0.0002306065,0.0002625638,0.0001430114,0.0002648111,0.0002841577,0.0005398168,0.0004661753],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0003897151,"about_ca_system_score_gemma":0.0002830178,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00028624,"about_ca_topic_score_gemma":0.001159996,"domain_scores_codex":[0.9999287,0.00001017268,0.000004987189,0.00001372974,0.00002072075,0.0000216058],"domain_scores_gemma":[0.9999539,0.000004400409,0.00001556303,0.000004080622,0.000009325505,0.00001279279],"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":[0.000321641,0.0003866578,0.0005106181,0.0003136496,0.00004799447,0.0003136732,0.00005981793,0.002375028,0.9646225,0.001012548,0.000814284,0.02922159],"study_design_scores_gemma":[0.0003686408,0.005979757,0.003146917,0.00003920646,0.0001030592,0.001228721,0.00003996941,0.002564945,0.9651273,0.0003332908,0.02103303,0.0000350404],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9589997,0.01224241,0.01652176,0.000617448,0.00008444581,0.0006263292,0.00192187,0.000383071,0.008602912],"genre_scores_gemma":[0.9717217,0.0093498,0.01040272,0.0002876067,0.00002837813,0.0001654927,0.002145589,0.00002891621,0.005869927],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001508076,"threshold_uncertainty_score":0.005045056,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.004394522481364531,"score_gpt":0.2205972269929805,"score_spread":0.216202704511616,"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."}}