Inhibition of organic cation transporter 3 activity by tyrosine kinase inhibitors.
drug-drug interaction
molecular descriptors
organic cation transporter
pharmacokinetics
tyrosine kinase inhibitor
Journal
Fundamental & clinical pharmacology
ISSN: 1472-8206
Titre abrégé: Fundam Clin Pharmacol
Pays: England
ID NLM: 8710411
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
revised:
21
01
2021
received:
25
11
2020
accepted:
27
01
2021
pubmed:
2
2
2021
medline:
4
1
2022
entrez:
1
2
2021
Statut:
ppublish
Résumé
Organic cation transporter (OCT) 3 (SLC22A3) is a widely expressed drug transporter, handling notably metformin and platinum derivatives, as well as endogenous compounds like monoamine neurotransmitters. OCT3 has been shown to be inhibited by a few marketed tyrosine kinase inhibitors (TKIs). The present study was designed to determine whether additional TKIs may interact with OCT3. For this purpose, the effects of 25 TKIs toward OCT3 activity were analyzed using OCT3-overexpressing HEK293 cells. 13/25 TKIs, each used at 10 µM, were found to behave as moderate or strong inhibitors of OCT3 activity, that is, they decreased OCT3-mediated uptake of the fluorescent dye 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide by at least 50% or 80%, respectively. This OCT3 inhibition was correlated to some molecular descriptors of TKIs, such as the percentage of H atoms and that of cationic forms at pH = 7.4. It was concentration-dependent, notably for brigatinib, ceritinib, and crizotinib, which exhibited low half maximal inhibitory concentration (IC
Substances chimiques
Organic Cation Transport Proteins
0
Organophosphorus Compounds
0
Protein Kinase Inhibitors
0
Pyrimidines
0
Sulfones
0
solute carrier family 22 (organic cation transporter), member 3
0
Crizotinib
53AH36668S
brigatinib
HYW8DB273J
ceritinib
K418KG2GET
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
919-929Informations de copyright
© 2021 Societe Francaise de Pharmacologie et de Therapeutique.
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