{"id":"W4405695055","doi":"10.1021/acs.jmedchem.4c02694","title":"Discovery of MDI-114215: A Potent and Selective LIMK Inhibitor To Treat Fragile X Syndrome","year":2024,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Genetics and Neurodevelopmental Disorders","field":"Biochemistry, Genetics and Molecular Biology","cited_by":8,"is_retracted":false,"has_abstract":true,"ca_institutions":"McGill University; Montreal Neurological Institute and Hospital","funders":"Medical Research Council","keywords":"Fragile X syndrome; Cofilin; Chemistry; Long-term potentiation; Kinome; Neuroscience; Allosteric regulation; Hippocampal formation; DYRK1A; Cell biology; Phosphorylation; Actin cytoskeleton; Cytoskeleton; Biochemistry; Biology; Receptor; Cell; Genetics","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":[0.0002108726,0.0005017522,0.0004018616,0.0005731625,0.000216522,0.0003741336,0.0004262495,0.0004988608,0.002004071],"category_scores_gemma":[0.00008929023,0.0001847162,0.0002655927,0.0002516146,0.0001442161,0.0002259593,0.0002339018,0.0006510758,0.0006801984],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0005212225,"about_ca_system_score_gemma":0.0003194231,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0007288956,"about_ca_topic_score_gemma":0.001621514,"domain_scores_codex":[0.9999391,0.000006399526,0.000005351825,0.00001098406,0.00002107159,0.00001706731],"domain_scores_gemma":[0.9999744,0.000002845845,0.000004410187,0.000001668802,0.000005075765,0.00001155812],"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":[0.000751054,0.0003532943,0.0003919017,0.0002792133,0.00007027442,0.0004784758,0.00005003456,0.0008350035,0.9299087,0.001095857,0.004527775,0.06125844],"study_design_scores_gemma":[0.001048879,0.002979059,0.005298743,0.00004011202,0.0001522673,0.001786413,0.00003655165,0.004107136,0.9290348,0.0002860266,0.05519258,0.00003743115],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9197959,0.02879317,0.01499074,0.003183874,0.0004277355,0.0008268271,0.003168699,0.001290335,0.02752283],"genre_scores_gemma":[0.9566944,0.01495404,0.01185983,0.000597209,0.00007182522,0.0002742571,0.002937289,0.00005266811,0.01255849],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.002004071,"threshold_uncertainty_score":0.006704211,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.004469366877787835,"score_gpt":0.2259945619584728,"score_spread":0.2215251950806849,"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."}}