Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/95467
DC Field | Value | Language |
---|---|---|
dc.contributor | Department of Applied Biology and Chemical Technology | en_US |
dc.creator | Wong, ILK | en_US |
dc.creator | Zhu, X | en_US |
dc.creator | Chan, KF | en_US |
dc.creator | Liu, Z | en_US |
dc.creator | Chan, CF | en_US |
dc.creator | Chow, TS | en_US |
dc.creator | Chong, TC | en_US |
dc.creator | Law, MC | en_US |
dc.creator | Cui, J | en_US |
dc.creator | Chow, LMC | en_US |
dc.creator | Chan, TH | en_US |
dc.date.accessioned | 2022-09-19T02:22:08Z | - |
dc.date.available | 2022-09-19T02:22:08Z | - |
dc.identifier.issn | 0022-2623 | en_US |
dc.identifier.uri | http://hdl.handle.net/10397/95467 | - |
dc.language.iso | en | en_US |
dc.publisher | American Chemical Society | en_US |
dc.rights | © 2021 American Chemical Society | en_US |
dc.rights | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jmedchem.1c00779. | en_US |
dc.title | Flavonoid monomers as potent, nontoxic, and selective modulators of the breast cancer resistance protein (ABCG2) | en_US |
dc.type | Journal/Magazine Article | en_US |
dc.identifier.spage | 14311 | en_US |
dc.identifier.epage | 14331 | en_US |
dc.identifier.volume | 64 | en_US |
dc.identifier.issue | 19 | en_US |
dc.identifier.doi | 10.1021/acs.jmedchem.1c00779 | en_US |
dcterms.abstract | We synthesize various substituted triazole-containing flavonoids and identify potent, nontoxic, and highly selective BCRP inhibitors. Ac18Az8, Ac32Az19, and Ac36Az9 possess m-methoxycarbonylbenzyloxy substitution at C-3 of the flavone moiety and substituted triazole at C-4′ of the B-ring. They show low toxicity (IC50 toward L929 > 100 μM), potent BCRP-inhibitory activity (EC50 = 1-15 nM), and high BCRP selectivity (BCRP selectivity over MRP1 and P-gp > 67-714). They inhibit the efflux activity of BCRP, elevate the intracellular drug accumulation, and restore the drug sensitivity of BCRP-overexpressing cells. Like Ko143, Ac32Az19 remarkably exhibits a 100% 5D3 shift, indicating that it can bind and cause a conformational change of BCRP. Moreover, it significantly reduces the abundance of functional BCRP dimers/oligomers by half to retain more mitoxantrone in the BCRP-overexpressing cell line and that may account for its inhibitory activity. They are promising candidates to be developed into combination therapy to overcome MDR cancers with BCRP overexpression. | en_US |
dcterms.accessRights | open access | en_US |
dcterms.bibliographicCitation | Journal of medicinal chemistry, 14 Oct. 2021, v. 64, no. 19, p. 14311-14331 | en_US |
dcterms.isPartOf | Journal of medicinal chemistry | en_US |
dcterms.issued | 2021-10-14 | - |
dc.identifier.scopus | 2-s2.0-85117161068 | - |
dc.identifier.pmid | 34606270 | - |
dc.identifier.eissn | 1520-4804 | en_US |
dc.description.validate | 202209 bcww | en_US |
dc.description.oa | Accepted Manuscript | en_US |
dc.identifier.FolderNumber | ABCT-0032 | - |
dc.description.fundingSource | RGC | en_US |
dc.description.fundingSource | Others | en_US |
dc.description.fundingText | PolyU | en_US |
dc.description.pubStatus | Published | en_US |
dc.identifier.OPUS | 61089386 | - |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Wong_Flavonoid_Monomers_As.pdf | Pre-Published version | 2.57 MB | Adobe PDF | View/Open |
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