{"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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.0000966944,0.0003367108,0.0002834985,0.0002063739,0.000146469,0.0001713933,0.0003212625,0.0002285354,0.001452943],"category_scores_gemma":[0.00009499231,0.0001337856,0.0001659884,0.0001567877,0.0001190467,0.0001424609,0.000194873,0.0003514527,0.0005394025],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002637443,"about_ca_system_score_gemma":0.0002334056,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.000492639,"about_ca_topic_score_gemma":0.001465429,"domain_scores_codex":[0.9999443,0.000005816849,0.000004729033,0.0000118421,0.0000108955,0.00002238744],"domain_scores_gemma":[0.9999735,0.000002438195,0.000007269256,0.000002282472,0.000004299173,0.00001016367],"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":[0.0003243353,0.0001861633,0.0001497977,0.0003391441,0.00002130188,0.0004245087,0.00009690074,0.003866802,0.9730507,0.001965373,0.00105985,0.01851503],"study_design_scores_gemma":[0.0003082736,0.003315612,0.002066881,0.00005189461,0.0000434865,0.0005403578,0.00004513716,0.006515477,0.9565859,0.0003400323,0.0301362,0.00005074892],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9492363,0.01029721,0.01995593,0.000413762,0.0001605725,0.0006026813,0.001520672,0.0004988867,0.0173141],"genre_scores_gemma":[0.9784579,0.006003557,0.00907845,0.0001681323,0.00002453281,0.000270333,0.000672144,0.00002812899,0.005296819],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.001452943,"threshold_uncertainty_score":0.00486064,"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."}}