{"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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.00006552129,0.0002638019,0.0001333226,0.0001086079,0.00006773336,0.000102204,0.0002408228,0.0001913682,0.000678324],"category_scores_gemma":[0.00005290898,0.00008825478,0.0001149823,0.00006819487,0.0001461664,0.0001311981,0.0001510297,0.0002559708,0.0003312022],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001756918,"about_ca_system_score_gemma":0.0002243883,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0004596224,"about_ca_topic_score_gemma":0.0008765344,"domain_scores_codex":[0.999974,0.000003578975,0.000001598394,0.000006704699,0.000006111443,0.000008024964],"domain_scores_gemma":[0.9999845,8.271791e-7,0.000004754956,9.735431e-7,0.000003016879,0.000005979826],"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":[0.0001138829,0.00005161223,0.0001759136,0.00008706412,0.000006518312,0.0001381003,0.00002481836,0.0003997593,0.9892615,0.0007563707,0.0002812199,0.008703168],"study_design_scores_gemma":[0.00008993862,0.001600146,0.001364696,0.00001105029,0.00002367865,0.0005558651,0.0000192493,0.001841925,0.9802743,0.0001570638,0.01404731,0.00001462368],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9687653,0.005607558,0.01519314,0.0004344264,0.00009070302,0.0001458245,0.000505315,0.0003301086,0.008927763],"genre_scores_gemma":[0.9874718,0.002558522,0.005527288,0.0001349493,0.00001243554,0.0000429284,0.0004513627,0.00001336488,0.003787368],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.000678324,"threshold_uncertainty_score":0.002269268,"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."}}