V-9302 |
Katalog-Nr.GC34852
One-Click Copy Product Info
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V-9302 ist ein kompetitiver Antagonist des Transmembran-Glutaminflusses. V-9302 zielt selektiv und stark auf den AminosÄuretransporter ASCT2 (SLC1A5) ab, nicht auf ASCT1. V-9302 hemmt die ASCT2-vermittelte Glutaminaufnahme (IC50=9,6 μM) in HEK-293-Zellen.
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Cas No.: 1855871-76-9
Sample solution is provided at 25 µL, 10mM.
V-9302 hydrochloride is a competitive antagonist of transmembrane glutamine flux. V-9302 hydrochloride selectively and potently targets the amino acid transporter ASCT2 (SLC1A5) not ASCT1[1].
V-9302 hydrochloride inhibits ASCT2-mediated glutamine uptake (IC50=9.6 µM) in HEK-293 cells. V-9302 hydrochloride inhibits ASCT2-mediated glutamine uptake in human cells in a concentration-dependent fashion. Treatment of HCC1806 cells with V-9302 hydrochloride resulted in a significant decrease in downstream levels including phosphorylated (P)-S6 and a moderate decrease in P-ERK levels, similar to knockdown of ASCT2[1].Pharmacological blockade of ASCT2 with V-9302 hydrochloride resulted in attenuated cancer cell growth and proliferation, increased cell death, and increased oxidative stress[1].The phosphorylation levels of the mTOR, S6K, and S6 proteins were reduced by treatment with 20 μM of V-9302 hydrochloride in SKOV3-TR cells, indicating that V-9302 hydrochloride effectively inhibited the mTORC1/S6K signaling pathway[2]. As the glutamine transporter inhibitor ，V-9302 hydrochloride suppresses tumor growth and increases T lymphocyte activation in a model of TNBC[5]
In vivo,steady-state plasma concentrations were achieved at 4 h post-administration with a half-life of approximately 6 h in healthy mice. Besides,using anhymic nude mice bearing HCT-116 or HT29 cell line xenografts, V-9302 hydrochloride prevented tumor growth. V-9302 hydrochloride led to significantly decreased expression of p-S6 in tumor tissue in both HCT-116 and HT29 xenografts. In addition to decreased p-S6 IHC staining, V-9302 hydrochloride treatment led to elevated levels of cleaved caspase 3[1]. In vivo xenograft tumor model of MDA-MB-231 cells, tumor growth was inhibited by V-9302 hydrochloride alone, and further inhibited by combination of V-9302 hydrochloride with other inhabitor[3].The combination of CB-839 and V-9302 hydrochloride elicits a strong growth inhibition in both SNU398 and MHCC97H xenograft models, while single-drug treatment showed modest anti-tumor effects[4]. ASCT2 inhibitor V-9302 hydrochloride may has influence in Alanine uptake in MRI[7]. Blockade of glutamine uptake using V9302 hydrochloride combined mTORC1/2 inhibitor AZD2014 blocking the interaction between HDAC3 and GS not only significantly delayed the tumor growth but also resulted in partial or even complete tumor regression [6]
References:
[1]. Schulte ML, Fu A, et,al. Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models. Nat Med. 2018 Feb;24(2):194-202. doi: 10.1038/nm.4464. Epub 2018 Jan 15. PMID: 29334372; PMCID: PMC5803339.
[2]. Kim G, Jang SK,et,al. Inhibition of Glutamine Uptake Resensitizes Paclitaxel Resistance in SKOV3-TR Ovarian Cancer Cell via mTORC1/S6K Signaling Pathway. Int J Mol Sci. 2022 Aug 6;23(15):8761. doi: 10.3390/ijms23158761. PMID: 35955892; PMCID: PMC9369036.
[3]. Zhou Q, Lin W, et,al.Neddylation inhibition induces glutamine uptake and metabolism by targeting CRL3SPOP E3 ligase in cancer cells. Nat Commun. 2022 May 31;13(1):3034. doi: 10.1038/s41467-022-30559-2. Erratum in: Nat Commun. 2022 Jun 14;13(1):3424. PMID: 35641493; PMCID: PMC9156729
[4]. Jin H, Wang S, et,al. A powerful drug combination strategy targeting glutamine addiction for the treatment of human liver cancer. Elife. 2020 Oct 5;9:e56749. doi: 10.7554/eLife.56749. PMID: 33016874; PMCID: PMC7535927.
[5]. Edwards DN, Ngwa VM, et,al. Selective glutamine metabolism inhibition in tumor cells improves antitumor T lymphocyte activity in triple-negative breast cancer. J Clin Invest. 2021 Feb 15;131(4):e140100. doi: 10.1172/JCI140100. PMID: 33320840; PMCID: PMC7880417.
[6]. Zhang HL, Chen P, et,al. Targeting mTORC2/HDAC3 Inhibits Stemness of Liver Cancer Cells Against Glutamine Starvation. Adv Sci (Weinh). 2022 Jul;9(20):e2103887. doi: 10.1002/advs.202103887. Epub 2022 Feb 20. PMID: 35187863; PMCID: PMC9284171.
[7]. Yang SH, Choi Y, et,al. MRI measurement of alanine uptake in a mouse xenograft model of U-87 MG glioblastoma. Magn Reson Imaging. 2022 Aug 24;93:189-194. doi: 10.1016/j.mri.2022.08.015. Epub ahead of print. PMID: 36029935.
| Cell experiment [1]: | |
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Cell lines |
HCC1806 cells |
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Preparation Method |
Cells were plated in 96-well plates for 24 h before the assay. Cells were treated with either vehicle or the indicated concentrations（25 μM） of V-9302 hydrochloride for 48 h |
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Reaction Conditions |
25 μM，48h |
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Applications |
Silencing of ASCT2 and V-9302 hydrochloride exposure in HCC1806 cells resulted in analogous downstream effects, including markedly decreased phosphorylated (p)-S6 levels and a modest decrease in p-ERK levels. |
| Animal experiment [2]: | |
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Animal models |
6-week-old female athymic nude mice |
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Preparation Method |
Chronic-exposure studies in tumor-bearing mice. Athymic nude mice (Hsd:Athymic nude-Foxn1nu) bearing HCT-116 (KRAS-G13D) or HT29 (BRAF-V600E) cell line xenografts were treated with 75 mg V-9302 hydrochloride per kg body weight per day for 21 d. |
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Dosage form |
75 mg V-9302 hydrochloride per kg body weight per day for 21 day |
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Applications |
V-9302 hydrochloride led to significantly decreased expression of p-S6 in tumor tissue in both HCT-116 and HT29 xenografts. In addition to decreased p-S6 IHC staining, V-9302 treatment led to elevated levels of cleaved caspase 3 in both HCT-116 and HT29 xenografts. |
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References: [1]. Schulte ML, Fu A, et,al. Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models. Nat Med. 2018 Feb;24(2):194-202. doi: 10.1038/nm.4464. Epub 2018 Jan 15. PMID: 29334372; PMCID: PMC5803339. |
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| Cas No. | 1855871-76-9 | SDF | |
| Canonical SMILES | O=C(O)[C@@H](N)CCN(CC1=CC=CC=C1OCC2=CC=CC(C)=C2)CC3=CC=CC=C3OCC4=CC=CC(C)=C4 | ||
| Formula | C34H38N2O4 | M.Wt | 538.68 |
| Löslichkeit | DMSO : 125 mg/mL (232.05 mM);Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8564 mL | 9.2819 mL | 18.5639 mL |
| 5 mM | 371.3 μL | 1.8564 mL | 3.7128 mL |
| 10 mM | 185.6 μL | 928.2 μL | 1.8564 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
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Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 5 reference(s) in Google Scholar.)