JPH203

Name: JPH203
Brand: Selleck Chemicals
SKU: S8667
Rating: 5 (2 reviews)

For research use only.

Catalog No.S8667 Synonyms: KYT-0353

2 publications

CAS No. 1037592-40-7

JPH203, a selective L-type amino acid transporter 1 inhibitor, shows a dramatic inhibition of leucine uptake (IC50=0.06 µM) and cell growth (IC50=4.1 µM) in human colon cancer cells (HT-29), human oral cancer cells (YD-38) and leukemic cells.

Selleck's JPH203 has been cited by 2 publications

Purity & Quality Control

Choose Selective Amino acid transporter Inhibitors

Biological Activity

Description

JPH203, a selective L-type amino acid transporter 1 inhibitor, shows a dramatic inhibition of leucine uptake (IC50=0.06 µM) and cell growth (IC50=4.1 µM) in human colon cancer cells (HT-29), human oral cancer cells (YD-38) and leukemic cells.

Targets

LAT1 ^[1]
(Cell-free assay)

In vitro

JPH203 completely and slightly inhibited the L-Leucine uptake in YD-38 cells (IC50 value: 0.79 μM) and NHOKs (IC50 value: >100 μM), respectively. JPH203 inhibited HT-29 cell growth, generating an apparent IC50 of 4.1 μM, but the JPH203 IC50 concentration (0.06 μM) needed to inhibit the L-Leucine uptake did not inhibit HT-29 cell growth, which represents a 68-fold difference in susceptibility^[1]. JPH203 activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL in Saos2 human osteosarcoma cells. JPH203 can distinguish relative abundance between LAT1 and LAT2. It has high selectivity for LAT1^[2]. JPH203 was metabolically stable in mouse, rat, dog, monkey and human liver microsomal incubations^[3]. JPH203 induces both G2/M and G0/G1 cell cycle arrest, as well as reduced the S phase accompanied by altered expression of the proteins in cell cycle progression: cyclin D1, CDK4, and CDK6^[4].

Assay

Methods	Test Index	PMID
Western blot	p53 / Bad / Bcl-2 / Bcl-xl / Bax / Bak / Cleaved caspase / Cleaved PARP ; PubMed: 29200902 Korean J Physiol Pharmacol Saos2 cells were treated with 3 mM JPH203 for 24 h. Cell lysate was prepared and analyzed by immunoblotting as described in METHODS. p70S6K / p-P70S6k / p-S6 / S6 / p-ERK / ERK / p-AKT / AKT'; PubMed: 30241549 J Exp Clin Cancer Res P-p70 S6 kinase, p-ERK and p-AKT levels were assayed in PTC cell lines. Cells were plated in triplicates using normal growth medium, after overnight incubation cells were washed and 0.125X EAA was added. Cells were treated with 10 μM JPH203 or DMSO as control and lysed after 24 h. p-GCN2 / GCN2 / p-EIF2α / EIF2α / ATF4 ; PubMed: 30784173 J Cell Mol Med Activity of the two AA sensing pathways GCN2 and mTORC1 were analysed by immunoblot in the absence or presence of either 20 or 30 µmol/L of JPH203. ERK1/2 served as a loading control (the experiment presented here is representative of at least three independent experiments)	29200902 30241549 30784173
Growth inhibition assay	Cell viability; PubMed: 29200902 Korean J Physiol Pharmacol Saos2 and FOB cells were treated with various concentrations of JPH203 (A, Saos2 cells; B, FOB cells) for 1-4 days. The cell viabilities were determined by MTT assays. The percentage cell viability was calculated as a ratio of the optical density at 570 nm of JPH203 treated cells and untreated control cells. The control cells were measured in the absence of JPH203 treatment. Each data point represents the mean±S.E.M. of four experiments. p<0.05 vs. control, p<0.01 vs. control and **p<0.001 vs. control.	29200902

In vivo

Daily intravenous administration of JPH203 (12.5 and 25 mg/kg) significantly inhibited tumor growth in KKU-213 cholangiocarcinoma cell xenografts in the nude mice model in a dose-dependent manner with no statistically significant change in the animal’s body weight and with no differences in the histology and appearance of the internal organs compared with the control group. Thus, JPH203 shows anti-tumor efficacy in nude mice bearing human cholangiocarcinom (CCA) cell xenografts without general toxicity^[4].

Protocol

Cell Research:

^[2]

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Cell lines: Saos2 human osteosarcoma cells
Concentrations: 100 µM
Incubation Time: 72 h
Method:
Colony formation assays are performed by seeding 300 cells/well into 6 well plates. After 24 h of growth, the cells are treated with 100 µM JPH203 for 72 h. The JPH203 treatment is removed and fresh medium is added. The cells are incubated for 10 days. Thereafter, medium is removed and the cells are washed with phosphate buffered saline (PBS) and fixed with 4% paraformaldehyde for 10 min at 4℃. Sequentially, the colonies are stained with 2% crystal violet for 10 min. Finally, colonies stained by crystal violet are washed with PBS and dried at room temperature, before imaged by a digital camera.

(Only for Reference)

Animal Research:

^[3]

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Animal Models: Sprague-Dawley rats
Dosages: 0.9-1.0 mg/kg
Administration: i.v.
(Only for Reference)

References

[4] Yothaisong S, et al. Tumour Biol. 2017, 39(3):1010428317694545.

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Solubility (25°C)

In vitro	DMSO	0.01 mg/mL (0.02 mM)
	Water	Insoluble
	Ethanol	Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download JPH203 SDF

Molecular Weight	472.32
Formula	C₂₃H₁₉Cl₂N₃O₄
CAS No.	1037592-40-7
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	KYT-0353
Smiles	C1=CC=C(C=C1)C2=NC3=CC(=CC(=C3O2)COC4=C(C=C(C=C4Cl)CC(C(=O)O)N)Cl)N

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

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JPH203