| http://purl.uniprot.org/citations/15805252 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15805252 | http://www.w3.org/2000/01/rdf-schema#comment | "Imatinib mesylate (signal transduction inhibitor 571, Gleevec) is a potent and selective tyrosine kinase inhibitor, which was shown to effectively inhibit platelet-derived growth factor-induced glioblastoma cell growth preclinically. However, in patients, a limited penetration of imatinib into the brain has been reported. Imatinib is transported in vitro and in vivo by P-glycoprotein (P-gp; ABCB1), which thereby limits its distribution into the brain in mice. Previously, imatinib was shown to potently inhibit human breast cancer resistance protein (BCRP; ABCG2). Here, we show that imatinib is efficiently transported by mouse Bcrp1 in transfected Madin-Darby canine kidney strain II (MDCKII) monolayers. Furthermore, we show that the clearance of i.v. imatinib is significantly decreased 1.6-fold in Bcrp1 knockout mice compared with wild-type mice. At t = 2 hours, the brain penetration of i.v. imatinib was significantly 2.5-fold increased in Bcrp1 knockout mice compared with control mice. We tested the hypothesis that P-gp and BCRP inhibitors, such as elacridar and pantoprazole, improve the brain penetration of imatinib. Firstly, we showed in vitro that pantoprazole and elacridar inhibit the Bcrp1-mediated transport of imatinib in MDCKII-Bcrp1 cells. Secondly, we showed that co-administration of pantoprazole or elacridar significantly reduced the clearance of i.v. imatinib in wild-type mice by respectively 1.7-fold and 1.5-fold. Finally, in wild-type mice treated with pantoprazole or elacridar, the brain penetration of i.v. imatinib significantly increased 1.8-fold and 4.2-fold, respectively. Moreover, the brain penetration of p.o. imatinib increased 5.2-fold when pantoprazole was co-administered in wild-type mice. Our results suggest that co-administration of BCRP and P-gp inhibitors may improve delivery of imatinib to malignant gliomas."xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-04-2416"xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://purl.uniprot.org/core/author | "Schinkel A.H."xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://purl.uniprot.org/core/author | "Schellens J.H."xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://purl.uniprot.org/core/author | "van Tellingen O."xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://purl.uniprot.org/core/author | "Cipriani G."xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://purl.uniprot.org/core/author | "Wielinga P."xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://purl.uniprot.org/core/author | "Pluim D."xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://purl.uniprot.org/core/author | "Breedveld P."xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15805252 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://purl.uniprot.org/core/pages | "2577-2582"xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://purl.uniprot.org/core/title | "The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients."xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://purl.uniprot.org/core/volume | "65"xsd:string |
| http://purl.uniprot.org/citations/15805252 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15805252 |
| http://purl.uniprot.org/citations/15805252 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15805252 |
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