{"id":"W4281393985","doi":"10.1021/acs.jmedchem.2c00173","title":"Illuminating the Dark: Highly Selective Inhibition of Serine/Threonine Kinase 17A with Pyrazolo[1,5- <i>a</i> ]pyrimidine-Based Macrocycles","year":2022,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Melanoma and MAPK Pathways","field":"Biochemistry, Genetics and Molecular Biology","cited_by":27,"is_retracted":false,"has_abstract":true,"ca_institutions":"","funders":"Structural Genomics Consortium; Deutsche Forschungsgemeinschaft","keywords":"Kinome; Chemistry; Serine; Pyrimidine; Kinase; Programmed cell death; Protein kinase A; Threonine; Biochemistry; Cell growth; In vitro; Drug discovery; Apoptosis; Cell biology; Cancer research; Phosphorylation; 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":[0.0001014008,0.0002827734,0.0002043595,0.0001354249,0.00008246625,0.0001748262,0.0001950996,0.0001459444,0.0008982837],"category_scores_gemma":[0.00008993111,0.00009588181,0.0001400038,0.00008825805,0.0001316787,0.0001864436,0.0002166099,0.0002598867,0.0002533744],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.000192505,"about_ca_system_score_gemma":0.000128984,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0003569952,"about_ca_topic_score_gemma":0.0009311218,"domain_scores_codex":[0.9999517,0.000008873949,0.000003673096,0.0000129423,0.000009269774,0.00001350057],"domain_scores_gemma":[0.9999701,0.000004313688,0.00001001441,0.000002504866,0.000003196448,0.000009849358],"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":[0.0003460107,0.00006120475,0.0001364727,0.0001309027,0.00001361725,0.0001630283,0.0000392968,0.001054623,0.9875975,0.0007502364,0.0003761709,0.009330858],"study_design_scores_gemma":[0.0001432145,0.001816284,0.001378835,0.00001705128,0.00002304491,0.0002991829,0.00002046587,0.00233146,0.9849311,0.0002253261,0.008794745,0.00001924999],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9812056,0.005743626,0.006530779,0.0001888682,0.0000747608,0.00007829144,0.0004165705,0.0002518686,0.005509704],"genre_scores_gemma":[0.9927684,0.002522119,0.002652144,0.00007587958,0.00001150916,0.00003438947,0.0001922563,0.00001409498,0.001729252],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.0008982837,"threshold_uncertainty_score":0.003005028,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.005414532205947249,"score_gpt":0.2062778087777506,"score_spread":0.2008632765718033,"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."}}