{"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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0004416927,0.0009752946,0.0008183511,0.001603492,0.0002186939,0.0007631199,0.0007550321,0.0009576935,0.002127264],"category_scores_gemma":[0.0005566632,0.0003834164,0.0004058878,0.001285654,0.0003861536,0.001160031,0.0005931833,0.002213782,0.002336915],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0008187423,"about_ca_system_score_gemma":0.0005713021,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0006508044,"about_ca_topic_score_gemma":0.001089731,"domain_scores_codex":[0.9998223,0.00002710684,0.00001531792,0.00003200351,0.00007780832,0.00002541944],"domain_scores_gemma":[0.9998571,0.00005411558,0.00002090713,0.000006587278,0.00004340006,0.00001802261],"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":[0.0001312139,0.0001514892,0.000126935,0.01301226,0.000108493,0.0003394271,0.00007961136,0.001258278,0.01440091,0.01698232,0.0652681,0.888141],"study_design_scores_gemma":[0.00001626207,0.00009375541,0.000208475,0.0007077125,0.00003602178,0.0004283795,0.00001553088,0.00015784,0.002446109,0.001057497,0.9948191,0.00001332773],"study_design_candidate":"not_applicable","study_design_consensus":null,"genre_codex":"review","genre_gemma":"review","genre_scores_codex":[0.0003910683,0.9958701,0.0005396194,0.000312728,0.0004861744,0.00001120491,0.00002991747,0.00002405929,0.002335196],"genre_scores_gemma":[0.002125698,0.9941585,0.0005058623,0.0003729269,0.0002091882,0.00002083173,0.00006024638,0.00000528244,0.002541492],"genre_candidate":"review","genre_consensus":"review","teacher_disagreement_score":0.002127264,"threshold_uncertainty_score":0.007116377,"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."}}