{"doi":"10.1093/noajnl/vdaa165","title":"A brain-penetrant microtubule-targeting agent that disrupts hallmarks of glioma tumorigenesis","abstract":"BACKGROUND: Glioma is sensitive to microtubule-targeting agents (MTAs), but most MTAs do not cross the blood brain barrier (BBB). To address this limitation, we developed the new chemical entity, ST-401, a brain-penetrant MTA. METHODS: Synthesis of ST-401. Measures of MT assembly and dynamics. Cell proliferation and viability of patient-derived (PD) glioma in culture. Measure of tumor microtube (TM) parameters using immunofluorescence analysis and machine learning-based workflow. Pharmacokinetics (PK) and experimental toxicity in mice. In vivo antitumor activity in the RCAS/tv-a PDGFB-driven glioma (PDGFB-glioma) mouse model. RESULTS: We discovered that ST-401 disrupts microtubule (MT) function through gentle and reverisible reduction in MT assembly that triggers mitotic delay and cell death in interphase. ST-401 inhibits the formation of TMs, MT-rich structures that connect glioma to a network that promotes resistance to DNA damage. PK analysis of ST-401 in mice shows brain penetration reaching antitumor concentrations, and in vivo testing of ST-401 in a xenograft flank tumor mouse model demonstrates significant antitumor activity and no over toxicity in mice. In the PDGFB-glioma mouse model, ST-401 enhances the therapeutic efficacies of temozolomide (TMZ) and radiation therapy (RT). CONCLUSION: Our study identifies hallmarks of glioma tumorigenesis that are sensitive to MTAs and reports ST-401 as a promising chemical scaffold to develop brain-penetrant MTAs.","journal":"Neuro-Oncology Advances","year":2020,"id":104409,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9612,"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":507114,"name":"Philippe Diaz","orcid":"0000-0002-2339-8803","position":1,"is_corresponding":false},{"id":305856,"name":"Patrick J. Cimino","orcid":"0000-0003-0441-4502","position":2,"is_corresponding":false},{"id":507115,"name":"Erik Jung","orcid":"0000-0002-5016-8202","position":3,"is_corresponding":false},{"id":507116,"name":"Cong Xu","orcid":"0000-0002-3661-0084","position":4,"is_corresponding":false},{"id":327225,"name":"Ernest Hamel","orcid":"0000-0003-3648-103X","position":5,"is_corresponding":false},{"id":507715,"name":"Michael Wagenbach","orcid":null,"position":6,"is_corresponding":false},{"id":507716,"name":"Debra K Kumasaka","orcid":null,"position":7,"is_corresponding":false},{"id":507117,"name":"Nicholas B. Wageling","orcid":"0000-0002-4598-4512","position":8,"is_corresponding":false},{"id":507118,"name":"Daniel Domínguez Azorín","orcid":"0000-0002-0002-4307","position":9,"is_corresponding":false},{"id":267520,"name":"Frank Winkler","orcid":"0000-0003-4892-6104","position":10,"is_corresponding":false},{"id":418058,"name":"Linda Wordeman","orcid":"0000-0002-9444-0650","position":11,"is_corresponding":false},{"id":226433,"name":"Eric C. Holland","orcid":"0000-0002-3792-7120","position":12,"is_corresponding":false},{"id":507119,"name":"Nephi Stella","orcid":"0000-0002-4780-8360","position":13,"is_corresponding":false},{"id":507113,"name":"Eric A. Horne","orcid":"0000-0002-9435-0962","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T22:43:22.755723Z","pmid":"33506204","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":[]}