{"id":"W4413808671","doi":"10.1021/acs.jmedchem.5c01584","title":"Hit-to-Lead Optimization of Acetazolamide-Based Bacterial Carbonic Anhydrase Inhibitors with Efficacy In Vivo for Treatment of Vancomycin-Resistant Enterococci Septicemia","year":2025,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Enzyme function and inhibition","field":"Biochemistry, Genetics and Molecular Biology","cited_by":6,"is_retracted":false,"has_abstract":true,"ca_institutions":"Purdue Pharma (Canada)","funders":"Horizon 2020 Framework Programme; National Institute of Allergy and Infectious Diseases; Ministero dell’Istruzione, dell’Università e della Ricerca; Purdue Institute for Drug Discovery; Purdue University","keywords":"Chemistry; Acetazolamide; In vivo; Carbonic anhydrase; Vancomycin; Microbiology; Antibiotics; Enterococcus; Vancomycin-Resistant Enterococci; Pharmacology; Enzyme; Bacteria; Biochemistry; Staphylococcus aureus; Internal medicine; Medicine; Biology","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":[],"consensus_categories":[],"category_scores_codex":[0.0001750151,0.0001444744,0.0003317875,0.00009482384,0.00001817562,0.000005041028,0.00008233065,0.0001242399,0.00003735536],"category_scores_gemma":[0.0001280779,0.0001131591,0.0001255758,0.0001414276,0.00005800562,0.000005707679,0.00001126614,0.00005690878,4.636063e-8],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001103963,"about_ca_system_score_gemma":0.0003466635,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.00000868914,"about_ca_topic_score_gemma":0.00001575343,"domain_scores_codex":[0.998962,0.00002536746,0.0005549187,0.0001535965,0.0001736797,0.0001303797],"domain_scores_gemma":[0.9990886,0.00003935194,0.0003974368,0.0001535206,0.0002470205,0.00007400331],"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":[0.005776719,0.0004334923,0.0007597859,0.0002041892,0.00007437066,0.000005261271,0.00004156207,0.008622837,0.9830601,9.218771e-7,0.0007721387,0.0002486216],"study_design_scores_gemma":[0.007426659,0.002504156,0.0002454856,0.0006048452,0.0001196896,0.000009229545,0.0001379983,0.0002606295,0.9865682,0.000001387744,0.002036182,0.00008551408],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9938866,0.0002485639,0.00494602,0.0002293683,0.0001670399,0.0001967879,0.0000192206,0.000002269346,0.0003040654],"genre_scores_gemma":[0.9978855,0.00004810773,0.001506417,0.00006131757,0.0002604238,0.00001031424,0.00004059391,0.00001136292,0.000176001],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.008362208,"threshold_uncertainty_score":0.4614492,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.006034865627572108,"score_gpt":0.2504769787130139,"score_spread":0.2444421130854418,"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."}}