{"id":"W4322011930","doi":"10.1016/j.ejmech.2023.115231","title":"Design, synthesis and characterisation of a novel type II B-RAF paradox breaker inhibitor","year":2023,"lang":"en","type":"article","venue":"European Journal of Medicinal Chemistry","topic":"Melanoma and MAPK Pathways","field":"Biochemistry, Genetics and Molecular Biology","cited_by":9,"is_retracted":false,"has_abstract":false,"ca_institutions":"","funders":"Genentech; Vlaamse regering; Innovative Medicines Initiative; Ontario Genomics Institute; European Federation of Pharmaceutical Industries and Associations; Merck KGaA; McGill University; Innovative Health Initiative; Ontario Genomics; Genome Canada; Fundação de Amparo à Pesquisa do Estado de São Paulo; Bayer; Pfizer","keywords":"Chemistry; Kinase; Vemurafenib; Protein kinase domain; MAPK/ERK pathway; Protein kinase A; V600E; Moiety; Allosteric regulation; Mutant; Stereochemistry; Cell biology; Biochemistry; Enzyme; Cancer research; Biology","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":[0.0002172375,0.0004904147,0.0003559747,0.0002653694,0.0002253536,0.0004848193,0.0006371742,0.0003830257,0.001662046],"category_scores_gemma":[0.0001565522,0.0001937253,0.0003319517,0.0001905303,0.0001377001,0.000318714,0.0002681058,0.0007922212,0.0007907569],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0004309607,"about_ca_system_score_gemma":0.000433055,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0005478831,"about_ca_topic_score_gemma":0.001127041,"domain_scores_codex":[0.999904,0.000009004611,0.000006996018,0.00002114136,0.00002642068,0.00003226296],"domain_scores_gemma":[0.9999534,0.000004451182,0.00001137104,0.000004796709,0.000009687844,0.00001635726],"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":[0.0003536855,0.0002271179,0.000198562,0.0001973797,0.00005178065,0.0002568885,0.00005048646,0.00193223,0.9717907,0.0008361064,0.0006330944,0.02347199],"study_design_scores_gemma":[0.0003538342,0.00212889,0.0007766534,0.00002184891,0.0001043279,0.0009038238,0.00003274004,0.003413472,0.9550427,0.0002394512,0.03694677,0.00003549881],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.8630779,0.0143674,0.1025999,0.001036491,0.0002879583,0.001850588,0.002216627,0.0008593465,0.01370381],"genre_scores_gemma":[0.9392588,0.007233338,0.03803691,0.0003330707,0.00003517959,0.0003736157,0.002145048,0.00006650547,0.01251765],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001662046,"threshold_uncertainty_score":0.0055601,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.02658339831722194,"score_gpt":0.2332749700659165,"score_spread":0.2066915717486946,"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."}}