{"doi":"10.1002/psp4.12552","title":"Multiscale Model Identifies Improved Schedule for Treatment of Acute Myeloid Leukemia <i>In Vitro</i> With the Mcl‐1 Inhibitor AZD5991","abstract":"Anticancer efficacy is driven not only by dose but also by frequency and duration of treatment. We describe a multiscale model combining cell cycle, cellular heterogeneity of B-cell lymphoma 2 family proteins, and pharmacology of AZD5991, a potent small-molecule inhibitor of myeloid cell leukemia 1 (Mcl-1). The model was calibrated using in vitro viability data for the MV-4-11 acute myeloid leukemia cell line under continuous incubation for 72 hours at concentrations of 0.03-30 μM. Using a virtual screen, we identified two schedules as having significantly different predicted efficacy and showed experimentally that a \"short\" schedule (treating cells for 6 of 24 hours) is significantly better able to maintain the rate of cell kill during treatment than a \"long\" schedule (18 of 24 hours). This work suggests that resistance can be driven by heterogeneity in protein expression of Mcl-1 alone without requiring mutation or resistant subclones and demonstrates the utility of mathematical models in efficiently identifying regimens for experimental exploration.","journal":"CPT Pharmacometrics & Systems Pharmacology","year":2020,"id":115094,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":540641,"name":"Haley Woods","orcid":null,"position":1,"is_corresponding":false},{"id":539734,"name":"Adriana E. Tron","orcid":"0000-0001-9506-2121","position":2,"is_corresponding":false},{"id":540642,"name":"Matthew A. Belmonte","orcid":null,"position":3,"is_corresponding":false},{"id":539735,"name":"J. Paul Secrist","orcid":"0000-0003-0447-6295","position":4,"is_corresponding":false},{"id":238700,"name":"Douglas Ferguson","orcid":null,"position":5,"is_corresponding":false},{"id":270246,"name":"Lisa Drew","orcid":"0000-0002-5912-8338","position":6,"is_corresponding":false},{"id":539736,"name":"Adrian J. Fretland","orcid":"0000-0003-4720-1662","position":7,"is_corresponding":false},{"id":539737,"name":"Bree B. Aldridge","orcid":"0000-0003-2236-1424","position":8,"is_corresponding":false},{"id":539738,"name":"Francis D. Gibbons","orcid":"0000-0003-1606-1740","position":9,"is_corresponding":false},{"id":540640,"name":"Ardeshir Goliaei","orcid":null,"position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T23:13:33.226937Z","pmid":"32860732","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}