{"doi":"10.3390/cancers15010029","title":"TP-0903 Is Active in Preclinical Models of Acute Myeloid Leukemia with TP53 Mutation/Deletion","abstract":"Acute myeloid leukemia (AML) with mutations in the tumor suppressor gene TP53 confers a dismal prognosis with 3-year overall survival of <5%. While inhibition of kinases involved in cell cycle regulation induces synthetic lethality in a variety of TP53 mutant cancers, this strategy has not been evaluated in mutant TP53 AML. Previously, we demonstrated that TP-0903 is a novel multikinase inhibitor with low nM activity against AURKA/B, Chk1/2, and other cell cycle regulators. Here, we evaluated the preclinical activity of TP-0903 in TP53 mutant AML cell lines, including a single-cell clone of MV4-11 containing a TP53 mutation (R248W), Kasumi-1 (R248Q), and HL-60 (TP 53 null). TP-0903 inhibited cell viability (IC50, 12−32 nM) and induced apoptosis at 50 nM. By immunoblot, 50 nM TP-0903 upregulated pChk1/2 and pH2AX, suggesting induction of DNA damage. The combination of TP-0903 and decitabine was additive in vitro, and in vivo significantly prolonged median survival compared to single-agent treatments in mice xenografted with HL-60 (vehicle, 46 days; decitabine, 55 days; TP-0903, 63 days; combination, 75 days) or MV4-11 (R248W) (51 days; 62 days; 81 days; 89 days) (p < 0.001). Together, these results provide scientific premise for the clinical evaluation of TP-0903 in combination with decitabine in TP53 mutant AML.","journal":"Cancers","year":2022,"id":274796,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":913048,"name":"Jack C. Stromatt","orcid":"0000-0001-8864-4617","position":1,"is_corresponding":false},{"id":943364,"name":"Sydney Fobare","orcid":"0000-0001-8417-6174","position":2,"is_corresponding":false},{"id":310484,"name":"Kevin M. Huang","orcid":"0000-0001-6561-3295","position":3,"is_corresponding":false},{"id":342105,"name":"Daelynn R. Buelow","orcid":"0000-0002-4413-5711","position":4,"is_corresponding":false},{"id":295287,"name":"Shelley Orwick","orcid":"0000-0002-4537-1409","position":5,"is_corresponding":false},{"id":370220,"name":"Jae Yoon Jeon","orcid":null,"position":6,"is_corresponding":false},{"id":943823,"name":"Robert H. Weber","orcid":null,"position":7,"is_corresponding":false},{"id":943824,"name":"B. M. Larsen","orcid":null,"position":8,"is_corresponding":false},{"id":295284,"name":"Alice S. Mims","orcid":"0000-0002-8971-2199","position":9,"is_corresponding":false},{"id":368836,"name":"Erin Hertlein","orcid":"0000-0001-8493-5679","position":10,"is_corresponding":false},{"id":35686,"name":"John C. Byrd","orcid":"0000-0001-9830-0711","position":11,"is_corresponding":false},{"id":342107,"name":"Sharyn D. Baker","orcid":"0000-0003-3062-3252","position":12,"is_corresponding":false},{"id":310489,"name":"Eric D. Eisenmann","orcid":"0000-0003-1176-675X","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T00:28:12.324621Z","pmid":"36612026","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":[]}