| pubmed-article:20345483 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20345483 | lifeskim:mentions | umls-concept:C1332002 | lld:lifeskim |
| pubmed-article:20345483 | lifeskim:mentions | umls-concept:C1704675 | lld:lifeskim |
| pubmed-article:20345483 | lifeskim:mentions | umls-concept:C1176020 | lld:lifeskim |
| pubmed-article:20345483 | lifeskim:mentions | umls-concept:C0206530 | lld:lifeskim |
| pubmed-article:20345483 | lifeskim:mentions | umls-concept:C0205464 | lld:lifeskim |
| pubmed-article:20345483 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:20345483 | pubmed:dateCreated | 2010-8-16 | lld:pubmed |
| pubmed-article:20345483 | pubmed:abstractText | Sunitinib malate (Sutent, SU11248) is a small-molecule multitargeted tyrosine kinase inhibitor (TKI) used for the treatment of renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumors. Some TKIs can overcome multidrug resistance conferred by ATP-binding cassette transporter, P-glycoprotein (P-gp)/ABCB1, multidrug resistance-associated protein 1 (MRP1)/ABCC1, and breast cancer resistance protein (BCRP)/ABCG2. Here, we analyzed the effects of sunitinib on P-gp and on wild-type and germ-line mutant BCRPs. Sunitinib remarkably reversed BCRP-mediated and partially reversed P-gp-mediated drug resistance in the respective transfectants. The in vitro vesicle transport assay indicated that sunitinib competitively inhibited BCRP-mediated estrone 3-sulfate transport and P-gp-mediated vincristine transport. These inhibitory effects of sunitinib were further analyzed in Q141K-, R482G-, R482S-, and F431L-variant BCRPs. Intriguingly, the F431L-variant BCRP, which is expressed by a germ-line mutant allele 1291T>C, was almost insensitive to both sunitinib- and fumitremorgin C (FTC)-mediated inhibition in a cell proliferation assay. Sunitinib and FTC did not inhibit (125)I-iodoarylazidoprazosin-binding to F431L-BCRP. Thus, residue Phe-431 of BCRP is important for the pharmacological interaction with sunitinib and FTC. Collectively, this is the first report showing a differential effect of a germ-line variation of the BCRP/ABCG2 gene on the pharmacological interaction between small-molecule TKIs and BCRP. These findings would be useful for improving our understanding of the pharmaceutical effects of sunitinib in personalized chemotherapy. | lld:pubmed |
| pubmed-article:20345483 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20345483 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20345483 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20345483 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:20345483 | pubmed:issn | 1349-7006 | lld:pubmed |
| pubmed-article:20345483 | pubmed:author | pubmed-author:SugimotoYoshi... | lld:pubmed |
| pubmed-article:20345483 | pubmed:author | pubmed-author:NoguchiKohjiK | lld:pubmed |
| pubmed-article:20345483 | pubmed:author | pubmed-author:KatayamaKazuh... | lld:pubmed |
| pubmed-article:20345483 | pubmed:author | pubmed-author:MitsuhashiJun... | lld:pubmed |
| pubmed-article:20345483 | pubmed:author | pubmed-author:KawaharaHaruk... | lld:pubmed |
| pubmed-article:20345483 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20345483 | pubmed:volume | 101 | lld:pubmed |
| pubmed-article:20345483 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20345483 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20345483 | pubmed:pagination | 1493-500 | lld:pubmed |
| pubmed-article:20345483 | pubmed:meshHeading | pubmed-meshheading:20345483... | lld:pubmed |
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| pubmed-article:20345483 | pubmed:meshHeading | pubmed-meshheading:20345483... | lld:pubmed |
| pubmed-article:20345483 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20345483 | pubmed:articleTitle | Pharmacological interaction with sunitinib is abolished by a germ-line mutation (1291T>C) of BCRP/ABCG2 gene. | lld:pubmed |
| pubmed-article:20345483 | pubmed:affiliation | Division of Chemotherapy, Keio University, Tokyo, Japan. | lld:pubmed |
| pubmed-article:20345483 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20345483 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
