Adeno-associated virus-mediated knockdown demonstrates the major role of hepatic Bcrp in the overall disposition of the active metabolite of the tyrosine kinase inhibitor regorafenib in mice.
Mice
Animals
ATP Binding Cassette Transporter, Subfamily G, Member 2
/ metabolism
Dependovirus
/ genetics
Tyrosine Kinase Inhibitors
ATP-Binding Cassette Transporters
/ genetics
Neoplasm Proteins
/ metabolism
Liver
/ metabolism
Protein Kinase Inhibitors
/ metabolism
RNA, Small Interfering
/ metabolism
Mice, Knockout
Active metabolite
Adeno-associated virus
Breast cancer resistance protein
Gene knockdown
Pharmacokinetics
Journal
Drug metabolism and pharmacokinetics
ISSN: 1880-0920
Titre abrégé: Drug Metab Pharmacokinet
Pays: England
ID NLM: 101164773
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
received:
09
02
2022
revised:
13
09
2022
accepted:
01
11
2022
pubmed:
2
2
2023
medline:
15
3
2023
entrez:
1
2
2023
Statut:
ppublish
Résumé
Breast cancer resistance protein (BCRP) is expressed on hepatic bile canalicular membranes; however, its impact on substrate drug disposition is limited. This study proposes an in vivo knockdown approach using adeno-associated virus encoding short hairpin RNA (shRNA) targeting the bcrp gene (AAV-shBcrp) to clarify the substrate, the overall disposition of which is largely governed by hepatic Bcrp. The disposition of the tyrosine kinase inhibitor, regorafenib, was first examined in bcrp gene knockout (Bcrp
Identifiants
pubmed: 36724604
pii: S1347-4367(22)00040-4
doi: 10.1016/j.dmpk.2022.100483
pii:
doi:
Substances chimiques
ATP Binding Cassette Transporter, Subfamily G, Member 2
0
Tyrosine Kinase Inhibitors
0
ATP-Binding Cassette Transporters
0
Neoplasm Proteins
0
Protein Kinase Inhibitors
0
RNA, Small Interfering
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
100483Informations de copyright
Copyright © 2022 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.