{"id":"W4412124121","doi":"10.1021/acs.jmedchem.5c01170","title":"Precision-Oriented Theophylline-Platinum(IV) Prodrugs: Eliciting Synthetic Lethality in BRCA1-Deficient Ovarian Cancer with Enhanced Efficacy and Reduced Toxicity <i>In Vitro</i> and <i>In Vivo</i>","year":2025,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Metal complexes synthesis and properties","field":"Medicine","cited_by":5,"is_retracted":false,"has_abstract":true,"ca_institutions":"Pancreas Centre (Canada)","funders":"Ministry of Science and Technology of the People's Republic of China; National Natural Science Foundation of China","keywords":"Olaparib; Synthetic lethality; Cisplatin; Prodrug; Chemistry; In vivo; Theophylline; Cancer research; Ovarian cancer; Pharmacology; DNA damage; DNA repair; PARP inhibitor; Poly ADP ribose polymerase; Cancer; Chemotherapy; Medicine; Internal medicine; Biology; Biochemistry; DNA; Polymerase","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":[0.001580689,0.000255286,0.0008691791,0.000175904,0.00005011003,0.00002173714,0.0001258854,0.0001226683,0.00005068444],"category_scores_gemma":[0.001003257,0.0001709982,0.00005583816,0.0004357201,0.0001881882,0.00007633804,0.00005807064,0.0007336201,1.432137e-7],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001674017,"about_ca_system_score_gemma":0.0003033519,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.000156893,"about_ca_topic_score_gemma":0.00004116594,"domain_scores_codex":[0.9976708,0.000132802,0.0009866658,0.0003666359,0.0005238329,0.000319248],"domain_scores_gemma":[0.9986205,0.0004725716,0.0003667001,0.0002228411,0.0001617823,0.0001556182],"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":[0.006838844,0.0002876546,0.002212294,0.0006633486,0.00004183212,0.00008953916,0.0008034364,0.00004253913,0.9800696,0.000005081489,0.00002100563,0.008924793],"study_design_scores_gemma":[0.005399196,0.0002044022,0.01470357,0.00798939,0.0001108922,0.0002252984,0.001208122,0.0003899214,0.9693161,0.000076472,0.0002007081,0.0001759054],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.991411,0.003788756,0.00007888124,0.001831286,0.00007588346,0.0003228565,0.000005805151,0.000007473778,0.002478111],"genre_scores_gemma":[0.9984297,0.000358753,0.0005755141,0.0003116973,0.0001234842,0.00001634383,0.000001127049,0.00001543058,0.0001679189],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.01249128,"threshold_uncertainty_score":0.6973104,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.01316967641941048,"score_gpt":0.2748016075001646,"score_spread":0.2616319310807541,"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."}}