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ABT-751 is an orally bioavailable microtubule-binding agent capable of overcoming MDR and proposed as an alternative to taxane-based therapies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This study compares ABT-751 to taxanes in vitro, utilizing seven melanoma cell line models, publicly available gene expression and drug sensitivity databases, a lung cancer cell line model of MDR drug efflux transporter overexpression (DLKP-A), and drug efflux transporter ATPase assays.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Melanoma cell lines exhibit a low but variable protein and RNA expression of drug efflux transporters P-gp, BCRP, and MDR3. Expression of P-gp and MDR3 correlates with sensitivity to taxanes, but not to ABT-751. The anti-proliferative IC<jats:sub>50<\/jats:sub> profile of ABT-751 was higher than the taxanes docetaxel and paclitaxel in the melanoma cell line panel, but fell within clinically achievable parameters. ABT-751 IC<jats:sub>50<\/jats:sub> was not impacted by P-gp-overexpression in DKLP-A cells, which display strong resistance to the P-gp substrate taxanes compared to DLKP parental controls. The addition of ABT-751 to paclitaxel treatment significantly decreased cell proliferation, suggesting some reversal of MDR. ATPase activity assays suggest that ABT-751 is a potential BCRP substrate, with the ability to inhibit P-gp ATPase activity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our study confirms that ABT-751 is active against melanoma cell lines and models of MDR at physiologically relevant concentrations, it inhibits P-gp ATPase activity, and it may be a BCRP and\/or MDR3 substrate. ABT-751 warrants further investigation alone or in tandem with other drug efflux transporter inhibitors for hard-to-treat MDR melanoma.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00280-023-04624-6","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T10:02:32Z","timestamp":1705399352000},"page":"427-437","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Evaluation of ABT-751, a novel anti-mitotic agent able to overcome multi-drug resistance, in melanoma cells"],"prefix":"10.1007","volume":"93","author":[{"given":"Thamir M.","family":"Mahgoub","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmet J.","family":"Jordan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amira F.","family":"Mahdi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronika","family":"Oettl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Huefner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norma","family":"O\u2019Donovan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Crown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1043-6169","authenticated-orcid":false,"given":"Denis M.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,1,16]]},"reference":[{"key":"4624_CR1","unstructured":"SEER*Explorer: an interactive website for SEER cancer statistics. 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A.F.M: Research funding (to institution): Puma Biotechnology. D.M.C: Research funding (to institution): Roche\/Genentech, WntResearch, Puma Biotechnology, Inc.;\u00a0Research materials: Sanofi. JC: Research funding (to institution): Eisai, Puma Biotechnology, Roche, Regeneron, Boehringer Ingelheim; Employment: OncoMark, Ltd.; Honoraria: Eisai, Puma Biotechnology; MSD Oncology, Pfizer, G1 Therapeutics; Novartis; Speaker\u2019s Bureau: Boehringer Ingelheim, Genomic Health, Roche, Pfizer; Shares: OncoMark Ltd; Travel and accommodation expenses: Pfizer, MSD, Abbvie, Astrazeneca, Novartis.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}