RSL3
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
IC50为100 nM。
RSL3(1S,3R-)是谷胱甘肽过氧化物酶4的抑制剂。
维持细胞氧化还原平衡对于细胞存活和组织稳态是至关重要的,因为活性氧的不平衡产生导致氧化应激和细胞死亡。抗氧化酶谷胱甘肽过氧化物酶4是氧化应激诱导的细胞死亡的重要调节剂。
体外:在急性淋巴细胞白血病细胞中,谷胱甘肽过氧化物酶(GPX)4抑制剂RSL3与Smac模拟物BV6一起诱导活性氧(ROS)依赖性细胞死亡。添加caspase抑制剂不能营救ROS诱导的细胞死亡,这表明RSL3诱导的细胞死亡是caspase非依赖性的。此外,铁螯合剂Deferoxamine显著抑制RSL3 / BV6诱导的细胞死亡,而不能营救Erastin / BV6诱导的细胞死亡,表明RSL3/BV6介导的细胞死亡依赖于铁而Erastin/BV6不依赖于铁。此外,ROS产生对于RSL3 / BV6和Erastin / BV6诱导的细胞死亡都是必需的。相比之下,遗传或药理抑制GPX4过表达引发的脂质过氧化可显著减少RSL3 / BV6诱导的细胞死亡。重要的是,抑制脂质过氧化可以防止RSL3/BV6刺激的ROS产生 [1]。
体内:目前尚无动物体内数据报道。
临床试验:到目前为止,RSL3仍处于临床前研究阶段。
参考文献:
[1] Dchert J,Schoeneberger H,Rohde K,Fulda S. RSL3 and Erastin differentially regulate redox signaling to promote Smac mimetic-induced cell death. Oncotarget.2016 Aug 29. doi: 10.18632/oncotarget.11687.
- 1. Schwartz, Hannah, et al. "In vitro Methods to Better Evaluate Drug Responses in Cancer." UMass Chan Medical School. September 8, 2022.
- 2. Tingting Liao, Xia Xu, et al. "DJ-1 upregulates the Nrf2/GPX4 signal pathway to inhibit trophoblast ferroptosis in the pathogenesis of preeclampsia." Sci Rep. 2022 Feb 21;12(1):2934. PMID: 35190654
- 3. Zongbo Wei, Caili Hao, et al. "Aging lens epithelium is susceptible to ferroptosis." Free Radic Biol Med. 2021 May 1;167:94-108. PMID: 33722625
- 4. Xinzhi Yang, Jiangang Liu, et al. "miR-18a promotes glioblastoma development by down-regulating ALOXE3-mediated ferroptotic and anti-migration activities." Oncogenesis. 2021 Feb 12;10(2):15. PMID: 33579899
- 5. Ali Ghoochani, En-Chi Hsu, et al. "Ferroptosis inducers are a novel therapeutic approach for advanced prostate cancer." Cancer Res. 2021 Mar 15;81(6):1583-1594. PMID: 33483372
- 6. Tong Zhang, Christin Bauer, et al. "Polyamine pathway activity promotes cysteine essentiality in cancer cells." Nature Metabolism (2020);03 August 2020. PMID: 32747794
- 7. Chu B, Kon N, et al. "ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway." Nat Cell Biol. 2019 May;21(5):579-591. PMID: 30962574
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 440.88 |
Cas No. | 1219810-16-8 |
Formula | C23H21ClN2O5 |
Solubility | insoluble in H2O; insoluble in EtOH; ≥125.4 mg/mL in DMSO |
Chemical Name | (1S,3R)-methyl 2-(2-chloroacetyl)-1-(4-(methoxycarbonyl)phenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate |
SDF | Download SDF |
Canonical SMILES | COC(C1=CC=C([C@@]2([H])C3=C(C4=CC=CC=C4N3)C[C@](N2C(CCl)=O)([H])C(OC)=O)C=C1)=O |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验 [1]: | |
细胞系 |
BJ-TERT/LT/ST/RASV12和DRD细胞 |
溶解方法 |
可溶于DMSO。若获取更高浓度的溶液,可在37°C下孵育10分钟,随后在超声波浴中摇匀。-20°C以下可储存数月。 |
反应条件 |
5 μg/ml,2天 |
应用 |
在BJ-TERT/LT/ST/RASV12和DRD细胞中,RSL3显示与致癌RAS的合成致死率。低至10 ng/ml的RSL3抑制细胞生长,在治疗后8小时开始杀死敏感细胞。用RSL3处理较长时间对缺乏致癌RAS的细胞的活力影响不大。在含有致癌性ras的肿瘤细胞中,RSL3诱导快速的非凋亡性细胞死亡。 |
动物实验 [2]: | |
动物模型 |
BJeLR细胞异种移植的无胸腺裸鼠 |
给药剂量 |
皮下注射,100 mg/kg,每周两次,持续2周。 |
应用 |
在异种移植模型中,RSL3阻止肿瘤生长。(1S,3R)-RSL3显著抑制肿瘤生长。(1S,3R)-RSL3通过诱导ferroptosis,显著减少肿瘤体积。腹腔注射高达400 mg/kg剂量的(1S,3R)-RSL3没有毒性,这表明(1S,3R)-RSL3具有良好的耐受性。 |
注意事项 |
由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。 |
References: [1]. Yang W S, Stockwell B R. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells[J]. Chemistry & biology, 2008, 15(3): 234-245. [2]. Yang W S, SriRamaratnam R, Welsch M E, et al. Regulation of ferroptotic cancer cell death by GPX4[J]. Cell, 2014, 156(1): 317-331. |
质量控制和MSDS
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