V-9302

Catalog No.S8818

V-9302 Chemical Structure

Molecular Weight(MW): 538.68

V-9302 is a competitive small molecule antagonist of transmembrane glutamine flux, that selectively and potently targets the amino acid transporter ASCT2 (SLC1A5) with an IC50 value of 9.6 μM for inhibition of glutamine uptake in HEK-293 cells.

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Biological Activity

Description V-9302 is a competitive small molecule antagonist of transmembrane glutamine flux, that selectively and potently targets the amino acid transporter ASCT2 (SLC1A5) with an IC50 value of 9.6 μM for inhibition of glutamine uptake in HEK-293 cells.
In vitro

V-9302 inhibits ASCT2-mediated glutamine uptake in human cells in a concentration-dependent fashion and exhibits a 100-fold improvement in potency (IC50 V-9302 = 9.6 µM) over gamma-L-glutamyl-p-nitroanilide (GPNA; IC50 = 1000 µM)[1].

Assay
Methods Test Index PMID
Western blot
ASCT2 / pS6 / S6 / pERK / ERK; 

PubMed: 29334372     


V-9302 exposure (25 µM, 48 hrs) exhibited a similar inhibition profile to silencing ASCT2 with shRNA in HCC1806 cells. 

29334372
Growth inhibition assay
Cell viability; 

PubMed: 29334372     


Direct comparison of V-9302 or CB-839 on the viability of human CRC cell lines. Drug incubated at concentrations shown for 48 hrs. Percent viability relative to vehicle control (MultiTox Glo assay); n = 3 independent experiments. P < 0.01 at 10 µM by Student’s t test. Error bars represent ± std. dev. *Estimated EC50. Error bars represent ± std. dev.

29334372
In vivo

Pharmacological blockade of ASCT2 with V-9302 results in attenuated cancer cell growth and proliferation, increases cell death, and increases oxidative stress, which collectively, contributes to anti-tumor responses in vitro and in murine models in vivo. The steady-state plasma concentrations are achieved 4 h post-administration, with a half-life of approximately 6 h in healthy mice. Following a single acute V-9302 exposure (4 h), plasma glucose levels are not significantly different than vehicle controls, yet plasma glutamine levels are elevated by approximately 50% in V-9302-treated mice compared to vehicle controls, likely a pharmacodynamic effect. Plasma glucose levels in mice chronically exposed to V-9302 or vehicle over a 21-day regimen are not significantly different, while plasma glutamine levels are slightly decreased[1].

Protocol

Cell Research:

[1]

+ Expand
  • Cell lines: HCC1806 cells
  • Concentrations: 25 µM
  • Incubation Time: 48 h
  • Method:

    HCC1806 cells are treated V-9302 (25 µM aqueous, 1% DMSO) for 48 h. Following treatment, cells are fixed with 70% methanol for 5-10 min. LC3B is visualized with 1:100 primary antibody at 37 ºC for 45 min followed by application of 1:600 secondary antibody at 37 ºC for 30 min and DAPI for 4 min.


    (Only for Reference)
Animal Research:

[1]

+ Expand
  • Animal Models: cell-line xenograft tumors (propagated in 6-week old, female athymic nude mice)
  • Formulation: PBS supplemented with 2% DMSO
  • Dosages: 75 mg/kg
  • Administration: IP
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (185.63 mM)
Water 100 mg/mL (185.63 mM)
Ethanol 100 mg/mL (185.63 mM)

* 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

Molecular Weight 538.68
Formula

C34H38N2O4

CAS No. 1855871-76-9
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID