{"id":"W4413436135","doi":"10.1016/j.ejmech.2025.118076","title":"Development of pyrazolo[1,5-a]pyrimidine based macrocyclic kinase inhibitors targeting AAK1","year":2025,"lang":"en","type":"article","venue":"European Journal of Medicinal Chemistry","topic":"Biochemical and Molecular Research","field":"Biochemistry, Genetics and Molecular Biology","cited_by":4,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Structural Genomics Consortium; National Institute of Allergy and Infectious Diseases; Innovative Medicines Initiative; Deutsche Krebshilfe; Wellcome Trust","keywords":"Chemistry; Pyrimidine; Kinase; Stereochemistry; Combinatorial chemistry; Biochemistry","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":[0.001371111,0.0001830321,0.0002545494,0.00006425317,0.0000661204,0.00001047665,0.0004428697,0.00008036703,0.00004861116],"category_scores_gemma":[0.0005266363,0.0001529471,0.0001660127,0.0001627255,0.0001847644,0.000002259729,0.0001833199,0.0003540564,0.000002473508],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00003112551,"about_ca_system_score_gemma":0.0003791675,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":5.009773e-7,"about_ca_topic_score_gemma":1.957304e-7,"domain_scores_codex":[0.9982492,0.000115984,0.0007526876,0.0002262377,0.0003929153,0.0002629894],"domain_scores_gemma":[0.9989474,0.00002008138,0.0003282751,0.0002136523,0.0002956006,0.0001949685],"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":[0.0002242325,0.0001127672,0.0001762686,0.0002497723,0.00008412026,0.0001061642,0.00003293177,0.0000163567,0.9828638,0.000001214557,0.004020968,0.01211145],"study_design_scores_gemma":[0.001164138,0.0001066344,0.0002079458,0.0003277171,0.00003018407,0.00003020383,0.0001351247,0.00001389395,0.935598,0.000003748349,0.06225978,0.0001226103],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9866606,0.003001986,0.003659755,0.0004406116,0.0001167241,0.0000565756,0.000002505718,0.000005326483,0.006055892],"genre_scores_gemma":[0.9945847,0.00004955188,0.004333343,0.0002265266,0.0003481809,0.000001075538,0.00003100973,0.00002242672,0.000403146],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.05823881,"threshold_uncertainty_score":0.6237003,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.009307123051497137,"score_gpt":0.2605608952207409,"score_spread":0.2512537721692438,"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."}}