{"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":"metacan-v3-hybrid-931329e0061c","candidate_categories":[],"consensus_categories":[],"category_scores_codex":[0.00007746591,0.0003218309,0.0001825688,0.0001657326,0.00008587805,0.0001018245,0.0001866748,0.00016392,0.00201169],"category_scores_gemma":[0.0000530123,0.0000866452,0.0002137485,0.00010413,0.0001213338,0.0002332748,0.000125079,0.0003682832,0.0004478357],"about_ca_system_candidate":false,"about_ca_system_consensus":false,"about_ca_system_score_codex":0.0001327139,"about_ca_system_score_gemma":0.000137736,"about_ca_topic_candidate":false,"about_ca_topic_consensus":false,"about_ca_topic_score_codex":0.0003221216,"about_ca_topic_score_gemma":0.0006076495,"domain_scores_codex":[0.9999685,0.000005571182,0.000002489003,0.000008175459,0.000005311295,0.000009914907],"domain_scores_gemma":[0.9999812,0.000002186316,0.000004922445,0.000001474499,0.000003047968,0.000007224397],"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":[0.0003516199,0.00009303619,0.0001598377,0.0002369926,0.00001833557,0.0001272729,0.00001748962,0.000342536,0.9907565,0.0003173142,0.000246272,0.007332828],"study_design_scores_gemma":[0.0002063312,0.007116132,0.00279969,0.000021428,0.0000938247,0.0007657365,0.00003854338,0.00133059,0.9733635,0.0001414994,0.01409864,0.00002404157],"study_design_candidate":"bench_or_experimental","study_design_consensus":"bench_or_experimental","genre_codex":"empirical","genre_gemma":"empirical","genre_scores_codex":[0.9766164,0.006761338,0.005633513,0.0003147512,0.000113295,0.0001517583,0.0009046491,0.0002187326,0.009285608],"genre_scores_gemma":[0.9904156,0.003494616,0.002240617,0.0001672338,0.00002321726,0.0000458332,0.0008190155,0.00001509704,0.002778852],"genre_candidate":"empirical","genre_consensus":"empirical","teacher_disagreement_score":0.00201169,"threshold_uncertainty_score":0.006729782,"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."}}