JPH203, a newly developed anti-cancer drug, shows a preincubation inhibitory effect on L-type amino acid transporter 1 function.
Adenocarcinoma
/ genetics
Antineoplastic Agents
/ pharmacology
Benzoxazoles
/ pharmacology
Colonic Neoplasms
/ genetics
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
/ methods
HT29 Cells
Humans
Large Neutral Amino Acid-Transporter 1
/ metabolism
Leucine
/ metabolism
Time Factors
Tyrosine
/ analogs & derivatives
Amino acid transporter
Anti-cancer drug
JPH203
LAT1
Preincubation inhibitory effects
Journal
Journal of pharmacological sciences
ISSN: 1347-8648
Titre abrégé: J Pharmacol Sci
Pays: Japan
ID NLM: 101167001
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
25
02
2019
revised:
26
03
2020
accepted:
07
06
2020
pubmed:
13
7
2020
medline:
30
10
2020
entrez:
13
7
2020
Statut:
ppublish
Résumé
JPH203 is a novel anti-cancer drug targeting L-type amino acid transporter 1 (LAT1), which plays a primary role in the uptake of essential amino acids in tumor cells. Although a co-incubation inhibitory effect of JPH203 has been shown in a conventional uptake assay, its preincubation inhibitory effects have remained undetermined. Therefore, we aimed to characterize the preincubation inhibitory effects of JPH203 on LAT1 function using leucine uptake assays in LAT1-positive human colon cancer HT-29 cells. Preincubation of the cells with JPH203 (0.3 μM for 120 min) decreased the activity level to 30% of that in dimethylsulfoxide-treated cells. Similarly, in time-dependency analysis, preincubation of HT-29 cells with 10 μM JPH203 for 30, 60, and 120 min decreased the leucine uptake activity (42%, 32%, and 28% of that in control cells, respectively). Furthermore, the IC
Identifiants
pubmed: 32653341
pii: S1347-8613(20)30063-3
doi: 10.1016/j.jphs.2020.06.006
pii:
doi:
Substances chimiques
2-amino-3-(4-((5-amino-2-phenylbenzo(d)oxazol-7-yl)methoxy)-3,5-dichlorophenyl)propanoic acid
0
Antineoplastic Agents
0
Benzoxazoles
0
Large Neutral Amino Acid-Transporter 1
0
SLC7A5 protein, human
0
Tyrosine
42HK56048U
Leucine
GMW67QNF9C
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
16-22Informations de copyright
Copyright © 2020 The Authors. Production and hosting by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors indicated no potential conflicts of interest.