R162 |
| رقم الكتالوجGC32750 |
R162 هو مثبط قوي للغلوتامات ديهيدروجينيز 1 (GDH1 / GLUD1) ، مع خصائص مضادة للسرطان
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 64302-87-0
Sample solution is provided at 25 µL, 10mM.
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R162 is a potent inhibitor of glutamate dehydrogenase 1 (GDH1)[1]. R162 has good antitumor activity and does not cause significant toxicity to normal tissues[2].
In vitro, treatment of LKB1-deficient non-small cell lung cancer (NSCLC) cells (A549, H157, and H460 cells) with R162 (40μM) significantly induced apoptosis, which was reversed by α-KG treatment[3]. Treatment of SUM44 and LCCTam cells with R162 (10μM) for 4h significantly induced the production of intracellular ROS[4].
In vivo, treatment of A549 cell xenograft mice with R162 (20mg/kg) by intraperitoneal injection for 45 days significantly reduced tumor metastasis[3]. Treatment of U251 cell xenograft mice with R162 (30mg/kg) by intraperitoneal injection for 35 days significantly inhibited tumor growth in mice[5]. R162 (20mg/kg) was intraperitoneally injected into H1299 cell xenograft mice for 35 days, which significantly inhibited the tumor growth and mass of the mice and suppressed the activity of GDH1 in tumor tissues[6].
References:
[1] Bian Y, Hou W, Chen X, et al. Glutamate dehydrogenase as a promising target for hyperinsulinism hyperammonemia syndrome therapy[J]. Current Medicinal Chemistry, 2022, 29(15): 2652-2672.
[2] Ren J, Zhou J, Liu H, et al. Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem[J]. Theranostics, 2021, 11(19): 9470.
[3] Jin L, Chun J, Pan C, et al. The PLAG1-GDH1 axis promotes anoikis resistance and tumor metastasis through CamKK2-AMPK signaling in LKB1-deficient lung cancer[J]. Molecular cell, 2018, 69(1): 87-99. e7.
[4] Young T A, Bahnassy S, Abalum T C, et al. Glutamate Transport Proteins and Metabolic Enzymes are Poor Prognostic Factors in Invasive Lobular Carcinoma[J]. bioRxiv, 2024.
[5] Zhang J, Wang G, Mao Q, et al. Glutamate dehydrogenase (GDH) regulates bioenergetics and redox homeostasis in human glioma[J]. Oncotarget, 2016, 5.
[6] Jin L, Li D, Alesi G N, et al. Glutamate dehydrogenase 1 signals through antioxidant glutathione peroxidase 1 to regulate redox homeostasis and tumor growth[J]. Cancer cell, 2015, 27(2): 257-270.
| Cell experiment [1]: | |
|
Cell lines |
A549、H460、H157 cells（LKB1-deficient cells） |
|
Preparation Method |
LKB1-deficient cells were cultured under detached conditions in the presence or absence of R162 (40μM) and methyl-α-KG (5mM for A549 and H460, 1mM for H157). Cells were cultured on 1% agar treated plate for 48h. Anoikis was determined by annexin V staining. |
|
Reaction Conditions |
40μM; 48h |
|
Applications |
Treatment with R162 significantly sensitized LKB1-deficient A549, H157, and H460 cells to anoikis induction, and this was fully rescued by α-KG treatment. |
| Animal experiment [2]: | |
|
Animal models |
Nude mice |
|
Preparation Method |
Nude mice (athymic nu/nu, female, 4-6 weeks old) were subcutaneously injected with 1×107 U251 cells harboring empty vector on the left flank, and cells with stable knockdown of GDH (or overexpression of GDH or Sirt4) on the right flank, respectively. To evaluate the efficacy of EGCG and R162, the drugs were administered from a day after U251 cells injection by daily intraperitoneal injection of 50mg/kg EGCG or 30mg/kg R162 for 35 days, respectively. Fifty percent of DMSO in PBS was as a diluent control. Tumor growth was recorded by measurement of two perpendicular diameters of the tumors. The tumors were harvested and weighed at the experimental endpoint. |
|
Dosage form |
30mg/kg; 35 days; i.p. |
|
Applications |
R162 treatment repressed U251 cell growth in vivo. |
|
References: |
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| Cas No. | 64302-87-0 | SDF | |
| Canonical SMILES | O=C1C2=C(C=CC=C2)C(C3=CC=C(CC=C)C(O)=C13)=O | ||
| Formula | C17H12O3 | M.Wt | 264.28 |
| الذوبان | DMSO : ≥ 100 mg/mL (378.39 mM) | 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. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.7839 mL | 18.9193 mL | 37.8387 mL |
| 5 mM | 756.8 μL | 3.7839 mL | 7.5677 mL |
| 10 mM | 378.4 μL | 1.8919 mL | 3.7839 mL |
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- Purity: >98.00%
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