{"id":"W4388825194","doi":"10.1021/acs.jmedchem.3c01271","title":"Discovery and Evaluation of C6-Substituted Pyrazolopyrimidine-Based Bisphosphonate Inhibitors of the Human Geranylgeranyl Pyrophosphate Synthase and Evaluation of Their Antitumor Efficacy in Multiple Myeloma, Pancreatic Ductal Adenocarcinoma, and Colorectal Cancer","year":2023,"lang":"en","type":"article","venue":"Journal of Medicinal Chemistry","topic":"Biochemical and Molecular Research","field":"Biochemistry, Genetics and Molecular Biology","cited_by":6,"is_retracted":false,"has_abstract":true,"ca_institutions":"McGill University Health Centre; Terry Fox Research Institute; McGill University","funders":"National Cancer Institute; Canadian Institutes of Health Research","keywords":"Chemistry; Cancer research; Bisphosphonate; Apoptosis; Cancer; Pancreatic cancer; Colorectal cancer; Pyrimidine metabolism; Pharmacology; Enzyme; Biochemistry; Purine; Internal medicine; Biology; Medicine","routes":{"ca_aff":true,"ca_fund":true,"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":[0.001670495,0.0001563313,0.0003443658,0.00006772981,0.00004766001,0.000008875972,0.0001361224,0.0001359287,0.000008207189],"category_scores_gemma":[0.0006746266,0.00010825,0.00008723175,0.0002327702,0.0005461859,0.00001296353,0.00009375386,0.0002004258,2.497217e-8],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00003896241,"about_ca_system_score_gemma":0.0004237576,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0001245029,"about_ca_topic_score_gemma":0.00002522084,"domain_scores_codex":[0.9981926,0.0001219464,0.0005253954,0.0002172534,0.0007789506,0.0001638476],"domain_scores_gemma":[0.9987506,0.00007832416,0.0004315764,0.0001470161,0.0005094932,0.0000829463],"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":[0.0005075557,0.00009509894,0.04930687,0.0003139538,0.00009311327,0.000006425453,0.0001053714,0.0001859669,0.948052,9.731233e-7,0.00001858777,0.001314075],"study_design_scores_gemma":[0.003504235,0.000125417,0.1987137,0.0004315707,0.0002031305,0.00003153787,0.0001415014,0.00212488,0.7946166,0.00002426775,0.00000313228,0.00008007939],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9881199,0.01134748,0.00000317421,0.0001455672,0.00005844791,0.0002821732,0.00002926247,0.00000157277,0.00001242583],"genre_scores_gemma":[0.9992771,0.0005867784,0.0000158352,0.000008101122,0.0000563267,0.00001288695,0.00002335188,0.00001275738,0.000006819849],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.1534354,"threshold_uncertainty_score":0.4414305,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.02872784293225333,"score_gpt":0.3079789370578118,"score_spread":0.2792510941255584,"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."}}