Nanvuranlat (JPH203)

Catalog No.S8667 Batch:S866703

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Technical Data

Formula

C23H19Cl2N3O4
Molecular Weight 472.32 CAS No. 1037592-40-7
Solubility (25°C)* In vitro DMSO 4 mg/mL (8.46 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Nanvuranlat (JPH203, KYT-0353, JPH-203SBECD), 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].
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 (from reference)

Cell Assay:

[2]
  • 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.
Animal Study:

[3]
  • Animal Models

    Sprague-Dawley rats

  • Dosages

    0.9-1.0 mg/kg

  • Administration

    i.v.

Selleck's Nanvuranlat (JPH203) has been cited by 20 publications

BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21 [ Microbiome, 2024, 12(1):157] PubMed: 39182099
BCKDK Modification Enhances the Anticancer Efficacy of CAR-T Cells by Reprogramming Branched Chain Amino Acid Metabolism [ Mol Ther, 2024, S1525-0016(24)00319-8] PubMed: 38734897
A rapid and simple non-radioactive assay for measuring uptake by solute carrier transporters [ Front Pharmacol, 2024, 15:1355507] PubMed: 38720778
Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect [ J Physiol Sci, 2024, 74(1):23] PubMed: 38561668
Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth [ Nat Commun, 2023, 14(1):6777] PubMed: 37880212
Targeting upregulation of the immunosuppressive activity of MDSCs with indirubin as a novel strategy to alleviate psoriasis [ Int Immunopharmacol, 2023, 123:110710] PubMed: 37531829
A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth [ Nat Metab, 2022, 4(6):672-682] PubMed: 35726026
Evaluation of 3-Borono-l-Phenylalanine as a Water-Soluble Boron Neutron Capture Therapy Agent [ Pharmaceutics, 2022, 14(5)1106] PubMed: 35631692
Construction and Functional Evaluation of a Three-Dimensional Blood-Brain Barrier Model Equipped With Human Induced Pluripotent Stem Cell-Derived Brain Microvascular Endothelial Cells [ Pharm Res, 2022, 39(7):1535-1547] PubMed: 35411503
Valine tRNA levels and availability regulate complex I assembly in leukaemia [ Nature, 2021, 10.1038/s41586-021-04244-1] PubMed: 34937946

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.