{"id":"W4380050493","doi":"10.1021/acsmedchemlett.3c00127","title":"Design and Synthesis of Pyrazole-Based Macrocyclic Kinase Inhibitors Targeting BMPR2","year":2023,"lang":"en","type":"article","venue":"ACS Medicinal Chemistry Letters","topic":"Phosphodiesterase function and regulation","field":"Biochemistry, Genetics and Molecular Biology","cited_by":14,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Genentech; Janssen Biotech; Innovative Medicines Initiative; H2020 Health; National and Kapodistrian University of Athens; Deutschen Konsortium für Translationale Krebsforschung; Ontario Genomics Institute; Takeda Pharmaceutical Company; European Federation of Pharmaceutical Industries and Associations; Merck KGaA; Ontario Genomics; Genome Canada; Bayer; Deutsches Krebsforschungszentrum; Bristol-Myers Squibb; Pfizer; McGill University; Boehringer Ingelheim","keywords":"BMPR2; Receptor; Tyrosine kinase; Kinase; Chemistry; Activin receptor; G protein-coupled receptor; Cancer research; Phosphorylation; Biochemistry; Pharmacology; Cell biology; Biology; Bone morphogenetic protein","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":[],"consensus_categories":[],"category_scores_codex":[0.0003241813,0.0001459263,0.0001468935,0.0000360677,0.00007114017,0.000008679562,0.00008693377,0.0001085544,0.00001436274],"category_scores_gemma":[0.0001553609,0.0001345879,0.0000469004,0.0001383424,0.0001722387,0.000003795272,0.00004343901,0.00007991602,0.000003301233],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00001351791,"about_ca_system_score_gemma":0.00003399585,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00000823895,"about_ca_topic_score_gemma":2.006162e-7,"domain_scores_codex":[0.9990917,0.00004143601,0.0002213671,0.0002664572,0.0001793335,0.0001997449],"domain_scores_gemma":[0.999518,0.00007217773,0.00011112,0.0001736442,0.00003644207,0.00008855265],"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":[0.00008774687,0.00001698839,0.000675733,0.000130867,0.00002663524,0.00001257645,0.00004102497,0.0006478346,0.9902349,2.143554e-7,0.006477087,0.001648355],"study_design_scores_gemma":[0.0004798401,0.00002618892,0.0005286799,0.00007429743,0.0000307647,0.000008237193,0.0001048101,0.0005205871,0.9963084,0.000003185266,0.001775447,0.0001395684],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.994928,0.0002221906,0.002971559,0.001592577,0.0001087718,0.00009053947,0.000004861542,0.0000322942,0.00004921203],"genre_scores_gemma":[0.9986358,0.00005490408,0.0003626398,0.0005069141,0.000222107,0.00002324514,0.0001098936,0.0000190002,0.00006546178],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.006073457,"threshold_uncertainty_score":0.5488335,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.008658515162420484,"score_gpt":0.2217936959449414,"score_spread":0.2131351807825209,"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."}}