Stereoselective Inhibition of High- and Low-Affinity Organic Cation Transporters.
drug enantiomers
organic cation transporters
solute carrier
stereoselectivity
transporter inhibition
Journal
Molecular pharmaceutics
ISSN: 1543-8392
Titre abrégé: Mol Pharm
Pays: United States
ID NLM: 101197791
Informations de publication
Date de publication:
04 Dec 2023
04 Dec 2023
Historique:
medline:
5
12
2023
pubmed:
14
11
2023
entrez:
14
11
2023
Statut:
ppublish
Résumé
Many drugs have chiral centers and are therapeutically applied as racemates. Thus, the stereoselectivity in their interactions with membrane transporters needs to be addressed. Here, we studied stereoselectivity in inhibiting organic cation transporters (OCTs) 1, 2, and 3 and the high-affinity monoamine transporters (MATs) NET and SERT. Selectivity by the inhibition of 35 pairs of enantiomers significantly varied among the three closely related OCTs. OCT1 inhibition was nonselective in almost all cases, whereas OCT2 was stereoselectively inhibited by 45% of the analyzed drugs. However, the stereoselectivity of the OCT2 was only moderate with the highest selectivity observed for pramipexole. The (
Identifiants
pubmed: 37962560
doi: 10.1021/acs.molpharmaceut.3c00691
pmc: PMC10698726
doi:
Substances chimiques
Organic Cation Transporter 1
0
Membrane Transport Proteins
0
Cations
0
Organic Cation Transport Proteins
0
Organic Cation Transporter 2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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