{"id":"W4292295879","doi":"10.1039/d2cs00387b","title":"Discovery of small molecule ligands for the von Hippel-Lindau (VHL) E3 ligase and their use as inhibitors and PROTAC degraders","year":2022,"lang":"en","type":"review","venue":"Chemical Society Reviews","topic":"Protein Degradation and Inhibitors","field":"Biochemistry, Genetics and Molecular Biology","cited_by":224,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"FP7 People: Marie-Curie Actions; FP7 Ideas: European Research Council; Biotechnology and Biological Sciences Research Council; European Commission; Directorate for Biological Sciences; European Federation of Pharmaceutical Industries and Associations; Horizon 2020 Framework Programme; University of Dundee; H2020 Marie Skłodowska-Curie Actions; Innovative Medicines Initiative; McGill University","keywords":"DNA ligase; Ubiquitin ligase; Small molecule; Chemistry; Computational biology; Combinatorial chemistry; Biochemistry; Stereochemistry; Ubiquitin; DNA; Biology; Gene","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":[0.000581091,0.0005182003,0.001165112,0.00001731479,0.000161523,0.00008699669,0.0003352135,0.0004344073,0.000006990431],"category_scores_gemma":[0.000542976,0.000309863,0.001303177,0.0001771102,0.0003218094,0.0000137305,0.0004486439,0.0003964857,8.919628e-7],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00003983417,"about_ca_system_score_gemma":0.0001628449,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00001088988,"about_ca_topic_score_gemma":0.000001064506,"domain_scores_codex":[0.9980466,0.00008452675,0.0007838697,0.0006669402,0.0001251035,0.0002929133],"domain_scores_gemma":[0.9985501,0.0001898621,0.0005694687,0.0005399922,0.00004046712,0.0001101074],"domain_codex":null,"domain_gemma":null,"domain_candidate":null,"domain_consensus":null,"study_design_codex":"design_other","study_design_gemma":"not_applicable","study_design_scores_codex":[0.00003879409,0.0001533635,0.000008490731,0.02247506,0.0005179775,5.150941e-7,0.0002756238,5.269231e-8,0.06841015,0.0000675377,0.02075233,0.8873001],"study_design_scores_gemma":[0.0002329618,0.0001092292,1.40587e-7,0.001422227,0.0002775667,0.00001543134,0.0000765458,0.000005877803,0.1424594,0.00001553583,0.8550744,0.000310666],"study_design_candidate":"design_other","study_design_consensus":null,"genre_codex":"review","genre_gemma":"review","genre_scores_codex":[0.004941913,0.9912725,0.0001160671,0.0001040848,0.000094909,0.003314777,0.0001278678,0.00001003664,0.00001782513],"genre_scores_gemma":[0.0001329653,0.9965275,0.000257245,0.0003641577,0.0002844213,0.001352241,0.0006245067,0.0000649383,0.0003920473],"genre_candidate":"review","genre_consensus":"review","teacher_disagreement_score":0.8869895,"threshold_uncertainty_score":0.9999353,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.05672681427050509,"score_gpt":0.2969829266204442,"score_spread":0.2402561123499391,"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."}}