Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/78684
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Eadie, L. | - |
dc.contributor.author | Saunders, V. | - |
dc.contributor.author | Hughes, T. | - |
dc.contributor.author | White, D. | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | Leukemia and Lymphoma, 2013; 54(3):569-578 | - |
dc.identifier.issn | 1042-8194 | - |
dc.identifier.issn | 1029-2403 | - |
dc.identifier.uri | http://hdl.handle.net/2440/78684 | - |
dc.description.abstract | Imatinib and nilotinib interact with ABCB1 and ABCG2. However, whether they are substrates or inhibitors is a source of conjecture. Here, in vitro, Bcr–Abl kinase inhibition was used to elucidate the impact of ABCB1/ABCG2 overexpression on imatinib and nilotinib transport. High levels of ABCB1 protein in K562-Dox cells resulted in a significantly increased 50% inhibitory concentration (IC₅₀) compared with parental K562 cells for imatinib (IC₅₀(IM); 9 µM to 19 µM, p = 0.002) and nilotinib (IC₅₀(NIL); 345 nM to 620 nM, p = 0.013). This difference was abrogated by ABCB1 inhibitors. However, overexpression of ABCG2 did not significantly increase IC₅₀(IM) or IC₅₀(NIL) or significantly decrease IC₅₀ upon ABCG2 inhibition. Inhibition of ABCB1 but not ABCG2 resulted in a substantial increase in intracellular nilotinib when used at 150 nM but no increase when used at 2 µM. Imatinib and nilotinib appear to be transported by ABCB1 but do not interact strongly with ABCG2. Furthermore, ABCB1 efflux of nilotinib may be concentration-dependent with transport occurring at clinically relevant concentrations. | - |
dc.description.statementofresponsibility | Laura N. Eadie, Verity A. Saunders, Timothy P. Hughes & Deborah L. White | - |
dc.language.iso | en | - |
dc.publisher | Taylor & Francis Ltd | - |
dc.rights | © 2013 Informa UK, Ltd. | - |
dc.source.uri | http://dx.doi.org/10.3109/10428194.2012.715345 | - |
dc.subject | CML | - |
dc.subject | nilotinib | - |
dc.subject | imatinib | - |
dc.subject | ABC transporters | - |
dc.title | Degree of kinase inhibition achieved in vitro by imatinib and nilotinib is decreased by high levels of ABCB1 but not ABCG2 | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.3109/10428194.2012.715345 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Eadie, L. [0000-0003-1912-7602] | - |
dc.identifier.orcid | Hughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509] | - |
dc.identifier.orcid | White, D. [0000-0003-4844-333X] | - |
Appears in Collections: | Aurora harvest 4 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.