{"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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.000191841,0.0003153804,0.0003480409,0.0002318902,0.0001003764,0.0001867471,0.0002500122,0.0002353092,0.0007181639],"category_scores_gemma":[0.00009323515,0.0001133671,0.0002376765,0.0002076632,0.0001166261,0.0001571186,0.0001251774,0.0003870931,0.000194644],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0002039004,"about_ca_system_score_gemma":0.000257241,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0005162155,"about_ca_topic_score_gemma":0.001295044,"domain_scores_codex":[0.9999225,0.00001787432,0.000008943482,0.00001255724,0.00002186431,0.0000162785],"domain_scores_gemma":[0.9999515,0.000005245674,0.00001424712,0.000005125551,0.0000100925,0.00001366453],"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":[0.0006011646,0.000362678,0.00043516,0.0002111827,0.00003382576,0.0001385473,0.00003117108,0.001101751,0.9779414,0.0002090219,0.0001315326,0.0188026],"study_design_scores_gemma":[0.0004432175,0.01126775,0.004609069,0.00001897886,0.0001476653,0.0007137377,0.00003010708,0.002282281,0.9714006,0.00007342486,0.008993453,0.00001986022],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9825351,0.01146885,0.00289558,0.000128235,0.00002962264,0.000175476,0.0004504696,0.00008048239,0.002236056],"genre_scores_gemma":[0.9859752,0.008126281,0.003331384,0.0000851177,0.00001420047,0.00007912407,0.0008031557,0.000008427489,0.001577091],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.0007181639,"threshold_uncertainty_score":0.002402544,"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."}}