R162
目录号 : GC32750
R162是一种有效的谷氨酸脱氢酶1（GDH1）抑制剂。
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.
R162是一种有效的谷氨酸脱氢酶1（GDH1）抑制剂[1]。R162具有良好的抗肿瘤活性，且不会对正常组织造成显著毒性[2]。
在体外，R162（40μM）处理LKB1缺陷的非小细胞肺癌（NSCLC）细胞（A549、H157和H460细胞），显著诱导了细胞凋亡，通过α-KG治疗可以逆转这一现象[3]。R162（10μM）处理SUM44和LCCTam细胞4h，显著诱导了细胞内ROS的产生[4]。
在体内，R162（20mg/kg）通过腹腔注射治疗A549细胞异种移植小鼠45天，显著减轻了肿瘤转移[3]。R162（30mg/kg）通过腹腔注射治疗U251细胞异种移植小鼠35天，显著抑制了小鼠体内肿瘤的生长[5]。R162（20mg/kg）通过腹腔注射治疗H1299细胞异种移植小鼠35天，显著抑制了小鼠的肿瘤生长和肿块，抑制了肿瘤组织中GDH1的活性[6]。
| 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: | |
| Cas No. | 64302-87-0 | SDF | |
| Canonical SMILES | O=C1C2=C(C=CC=C2)C(C3=CC=C(CC=C)C(O)=C13)=O | ||
| 分子式 | C17H12O3 | 分子量 | 264.28 |
| 溶解度 | DMSO : ≥ 100 mg/mL (378.39 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.7839 mL | 18.9193 mL | 37.8387 mL |
| 5 mM | 0.7568 mL | 3.7839 mL | 7.5677 mL |
| 10 mM | 0.3784 mL | 1.8919 mL | 3.7839 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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Quality Control & SDS
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- Purity: >98.00%
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