{"id":"W4400190355","doi":"10.1021/acs.jmedchem.4c00761","title":"Discovery of a Highly Potent and Selective HDAC8 Degrader: Advancing the Functional Understanding and Therapeutic Potential of HDAC8","year":2024,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Histone Deacetylase Inhibitors Research","field":"Biochemistry, Genetics and Molecular Biology","cited_by":16,"is_retracted":false,"has_abstract":true,"ca_institutions":"Princess Margaret Cancer Centre; University Health Network","funders":"National Institute of Neurological Disorders and Stroke; Washington University School of Medicine in St. Louis; Florida Department of Health; National Institutes of Health; National Science Foundation","keywords":"HDAC8; Chemistry; HDAC3; Acetylation; Histone deacetylase; Biochemistry; Histone; Gene","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":[0.0003072772,0.0003773213,0.0003281232,0.0001399798,0.0001071658,0.0003483676,0.0002504395,0.0003349025,0.000771784],"category_scores_gemma":[0.000123949,0.000151105,0.0002437575,0.0001185481,0.0001937264,0.000265379,0.000263204,0.000555459,0.0003988498],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0003678286,"about_ca_system_score_gemma":0.0002404119,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0002582129,"about_ca_topic_score_gemma":0.0004899619,"domain_scores_codex":[0.9998782,0.00001637064,0.00001083483,0.00002633708,0.00004027977,0.00002792079],"domain_scores_gemma":[0.999936,0.000005005523,0.00001950055,0.000009020147,0.00001135207,0.00001905599],"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":[0.0001210353,0.00004565245,0.0002733677,0.0000993826,0.00001562595,0.0001201533,0.00002206682,0.0002635632,0.9895458,0.0004586606,0.0002200748,0.008814679],"study_design_scores_gemma":[0.00004901414,0.0005890269,0.0008970088,0.000005596318,0.00001972265,0.0007541594,0.00001563418,0.0008058964,0.9887129,0.00006392936,0.008078747,0.000008415317],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9440079,0.01543438,0.03207195,0.0006673686,0.00009096217,0.0002429413,0.0006569845,0.0002907737,0.006536806],"genre_scores_gemma":[0.9781201,0.005475674,0.01201214,0.000172495,0.00003822509,0.0000528469,0.0006139401,0.00002263887,0.003491829],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.000771784,"threshold_uncertainty_score":0.002668858,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01429968898692268,"score_gpt":0.2631644869986211,"score_spread":0.2488647980116984,"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."}}