{"id":"W4409890102","doi":"10.1158/1535-7163.mct-24-0998","title":"A Novel Squaramide Derivative, HR-19011, Induces the Integrated Stress Response via the HRI–eIF2α–ATF4 Pathway, Effectively Inhibiting Hematologic Malignancies","year":2025,"lang":"en","type":"article","venue":"Molecular Cancer Therapeutics","topic":"Endoplasmic Reticulum Stress and Disease","field":"Biochemistry, Genetics and Molecular Biology","cited_by":3,"is_retracted":false,"has_abstract":true,"ca_institutions":"Nexen (Canada)","funders":"Ministry of Science and ICT, South Korea; Korea Drug Development Fund; National Research Foundation","keywords":"Integrated stress response; ATF4; mTORC1; Cancer research; eIF2; Biology; Cell cycle; Cell growth; P70-S6 Kinase 1; Phosphorylation; Signal transduction; Unfolded protein response; Cell biology; Apoptosis; Translation (biology); PI3K/AKT/mTOR pathway; Endoplasmic reticulum; Biochemistry; Gene; Messenger RNA","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":["metaepi_narrow"],"consensus_categories":[],"category_scores_codex":[0.0003956375,0.000413277,0.0002919924,0.00006748459,0.0004115972,0.0001289019,0.0006046076,0.000227313,0.00001104803],"category_scores_gemma":[0.0001994424,0.0002497706,0.000228321,0.0004345491,0.0004596789,0.000008802021,0.0002661241,0.0003282522,0.000002927418],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.00007317381,"about_ca_system_score_gemma":0.0004190282,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0001997621,"about_ca_topic_score_gemma":0.0001075079,"domain_scores_codex":[0.9977778,0.0005386157,0.000368372,0.0005559127,0.0002708473,0.0004884693],"domain_scores_gemma":[0.998593,0.0002104473,0.0002133314,0.0006583851,0.0002552373,0.00006958996],"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":[0.000694719,0.0001488836,0.001054613,0.00005677707,0.0003788492,0.00002306984,0.0002791951,0.0005630082,0.9930261,0.0008028449,0.0001159573,0.00285599],"study_design_scores_gemma":[0.0009559398,0.0001579252,0.003001236,0.0002065719,0.0001419419,0.00001819506,0.001015461,0.0004295734,0.9873159,0.0003213567,0.006095422,0.0003404799],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9651429,0.009563547,0.02137941,0.002523905,0.0002284692,0.0006806889,0.0001444475,0.00004229071,0.0002943398],"genre_scores_gemma":[0.993484,0.0003009533,0.0001690623,0.005309261,0.00005111931,0.0004014561,0.00005018732,0.00004193526,0.0001920752],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.02834104,"threshold_uncertainty_score":0.9999955,"prediction_status":"machine_predicted_unvalidated"},"machine_scores":{"provisional":true,"baseline":true,"maturity_gate_passed":false,"score_opus":0.0157589818069036,"score_gpt":0.2766060427206724,"score_spread":0.2608470609137688,"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."}}