{"id":"W2417066645","doi":"10.1021/acs.jmedchem.5b00597","title":"Discovery of 1-{4-[3-Fluoro-4-((3 <i>S</i> ,6 <i>R</i> )-3-methyl-1,1-dioxo-6-phenyl-[1,2]thiazinan-2-ylmethyl)-phenyl]-piperazin-1-yl}-ethanone (GNE-3500): a Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C (RORc or RORγ) Inverse Agonist","year":2015,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Psoriasis: Treatment and Pathogenesis","field":"Immunology and Microbiology","cited_by":59,"is_retracted":false,"has_abstract":true,"ca_institutions":"Discovery Centre","funders":"National Center for Research Resources; National Institutes of Health","keywords":"RAR-related orphan receptor gamma; Chemistry; Orphan receptor; ADME; Potency; Agonist; Stereochemistry; Inverse agonist; Pharmacology; Retinoic acid; Receptor; Nuclear receptor; Selectivity; In vitro; Biochemistry","routes":{"ca_aff":true,"ca_fund":false,"ca_venue":false,"about_ca":false,"invisible_to_affiliation_only":false},"retraction":null,"screen":null,"direct_labels":[],"prediction":{"model_version":"codex-gemma-dda1882f352a","candidate_categories":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.002384235,0.0007961047,0.001837879,0.000262387,0.0002746952,0.00005883294,0.0006967858,0.001061171,0.0007015113],"category_scores_gemma":[0.001749289,0.0006024686,0.0004852892,0.000829325,0.001021527,0.0005478469,0.0002054676,0.001296467,0.0001089826],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.000395603,"about_ca_system_score_gemma":0.001622326,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0001583228,"about_ca_topic_score_gemma":0.00002614934,"domain_scores_codex":[0.9953614,0.0006325673,0.001875938,0.0007446539,0.0005050867,0.0008803198],"domain_scores_gemma":[0.9947317,0.0005208207,0.002809905,0.0006008827,0.0009507253,0.0003859391],"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":[0.006049171,0.0005833994,0.004531258,0.0003235462,0.00131477,0.0001836792,0.0009262779,0.000002097393,0.9247639,0.000005603367,0.05644318,0.00487307],"study_design_scores_gemma":[0.008902847,0.001661869,0.0004006649,0.0008458832,0.001047186,0.002025548,0.001949052,0.000002154533,0.9592506,0.0001057921,0.02318538,0.0006230171],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9684908,0.02607217,0.00005321494,0.001006854,0.001875693,0.0003406198,0.0002033083,0.0000690141,0.001888339],"genre_scores_gemma":[0.9722325,0.006095005,0.002279717,0.0003390611,0.0007065592,0.00002749696,0.0003214158,0.0001253175,0.01787299],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.03448666,"threshold_uncertainty_score":0.9996427,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01761445717632747,"score_gpt":0.2391956362803825,"score_spread":0.221581179104055,"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."}}