TFEB activator 1
(Synonyms: (1E,4E)-1,5-二(2-甲氧基)-1,4-二烯基-3-戊酮,Curcumin analog C1) 目录号 : GC39530
TFEB activator 1是一种口服有效、不依赖mTOR的TFEB激活剂，能够显著促进Flag-TFEB的核易位，EC50值为2167nM。
Cas No.:39777-61-2
Sample solution is provided at 25 µL, 10mM.
TFEB activator 1 is an orally effective, mTOR-independent activator of TFEB that significantly promotes the nuclear translocation of Flag-TFEB with an EC50 of 2167nM[1]. Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy that coordinates cellular responses to nutrient availability and stress[2]. Once activated, TFEB induces lysosomal and autophagy gene expression, and enhances cellular clearance of aggregates and damaged organelles to maintain metabolic homeostasis[3]. TFEB activator 1 is commonly used in research on neurodegenerative diseases, such as Alzheimer's disease[4][5].
In vitro, TFEB activator 1 (1μM; 12h pretreatment; 15min co-treatment; 6h incubation) enhanced TFEB nuclear translocation, increased LC3B-II and SQSTM1/p62 protein levels, improved cell viability, prevented apoptosis, and promoted mitophagy in 6-OHDA/AA-treated SH-SY5Y cells[6].
References:
[1] Song JX, Sun YR, Peluso I, et al. A novel curcumin analog binds to and activates TFEB in vitro and in vivo independent of MTOR inhibition. Autophagy. 2016;12(8):1372-1389.
[2] Settembre C, Di Malta C, Polito VA, et al. TFEB links autophagy to lysosomal biogenesis. Science. 2011;332(6036):1429-1433.
[3] Franco-Juárez B, Coronel-Cruz C, Hernández-Ochoa B, et al. TFEB; Beyond Its Role as an Autophagy and Lysosomes Regulator. Cells. 2022;11(19):3153.
[4] Xie YQ, Zhu L, Wang XT.TFEB activator 1 enhances autophagic degradation of oligomeric amyloid-β in microglia. Sheng Li Xue Bao. 2024;76(3):365-375
[5] Perrone L, Squillaro T, Napolitano F, Terracciano C, Sampaolo S, Melone MAB. The Autophagy Signaling Pathway: A Potential Multifunctional Therapeutic Target of Curcumin in Neurological and Neuromuscular Diseases. Nutrients. 2019;11(8):1881.
[6] Zhuang XX, Wang SF, Tan Y, et al. Pharmacological enhancement of TFEB-mediated autophagy alleviated neuronal death in oxidative stress-induced Parkinson's disease models. Cell Death Dis. 2020;11(2):128.
[7] Song JX, Malampati S, Zeng Y, et al. A small molecule transcription factor EB activator ameliorates beta-amyloid precursor protein and Tau pathology in Alzheimer's disease models. Aging Cell. 2020;19(2):e13069.
TFEB activator 1是一种口服有效、不依赖mTOR的TFEB激活剂，能够显著促进Flag-TFEB的核易位，EC50值为2167nM[1]。转录因子EB（TFEB）是溶酶体生物发生和自噬的主要调控因子，可协调细胞对营养供应和应激的反应[2]。TFEB被激活后，可诱导溶酶体和自噬基因表达，增强细胞内聚物和受损细胞器的清除，从而维持代谢稳态[3]。TFEB activator 1常用于神经退行性疾病，如阿尔茨海默病的研究[4][5]。
在体外，TFEB activator 1（1μM；12小时预处理；15分钟共处理；6小时孵育）可增强6-OHDA/AA处理的SH-SY5Y细胞中TFEB的核易位，增加LC3B-II和SQSTM1/p62蛋白水平，提高细胞活力，抑制细胞凋亡，并促进线粒体自噬[6]。
在体内，TFEB activator 1（10mg/kg/天；灌胃；4个月）可减少5xFAD小鼠的全长APP、CTF-α/β和Aβ病理改变，增加TFEB核易位及自噬-溶酶体标志物（LC3B-II、LAMP1、CTSD），并恢复突触可塑性和记忆缺陷[7]。
| Cell experiment [1]: | |
Cell lines | SH-SY5Y cells |
Preparation Method | SH-SY5Y cells were maintained in DMEM/F-12 Media containing 10% fetal bovine serum in a 5% CO2 atmosphere at 37℃. Mycoplasma contamination testing status was negative. The cells were pretreated with TFEB activator 1 for 12h, and then treated with 6-OHDA/AA in the presence or absence of TFEB activator 1 for 15min, after which the medium was removed and replaced with DMEM F12 with or without TFEB activator 1 for another 6h. Mitochondrial membrane potential was determined by flow cytometer. The intralysosomal PH was estimated using LysoSensor and LysoTracker. Cell viability was determined by CCK8 assay. The apoptosis of the SH-SY5Y cells was determined with Annexin V/propidium iodide (PI) staining kit by flow cytometry. Cells were collected for Western blot analysis. |
Reaction Conditions | 1μM; 12h pretreatment; 15min co-treatment; 6h incubation |
Applications | TFEB activator 1 increased LC3B-II and SQSTM1/p62 protein levels, improved cell viability, and promoted mitophagy in 6-OHDA/AA-treated SH-SY5Y cells. |
| Animal experiment [2]: | |
Animal models | 5xFAD mice |
Preparation Method | 5xFAD mice were maintained at 23±2°C and 60±15% relative humidity with free access to feed and water. Two-month-old 5xFAD mice (male and female, n=10-14 per group) were treated daily with vehicle (1% CMC-Na) or TFEB activator 1 (10mg/kg) in 1% CMC-Na by oral gavage for 4 months. Contextualfear conditioning (CFC) was used to evaluate the fear memory reconsolidation of 5xFAD mice after treatment. After decapitation, mouse brain was quickly dissected and placed in sucrose-substituted ice-cold artificial cerebrospinal fluid for Electrophysiological recordings with microelectrode array recording system. And half brain tissues were lysed for Western blotting analysis and fixed for Immunohistochemistry analysis. |
Dosage form | 10mg/kg/day;oral gavage; 4 months |
Applications | TFEB activator 1 reduced full-length APP, CTF-α/β, and Aβ pathology, increased TFEB nuclear translocation and autophagy-lysosome markers (LC3B-II, LAMP1, CTSD), and restored synaptic plasticity and memory deficits in 5xFAD mice. |
References: | |
| Cas No. | 39777-61-2 | SDF | |
| 别名 | (1E,4E)-1,5-二(2-甲氧基)-1,4-二烯基-3-戊酮,Curcumin analog C1 | ||
| Canonical SMILES | O=C(/C=C/C1=CC=CC=C1OC)/C=C/C2=CC=CC=C2OC | ||
| 分子式 | C19H18O3 | 分子量 | 294.34 |
| 溶解度 | DMSO: 125 mg/mL (424.68 mM) | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
| 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 | 3.3974 mL | 16.9872 mL | 33.9743 mL |
| 5 mM | 679.5 μL | 3.3974 mL | 6.7949 mL |
| 10 mM | 339.7 μL | 1.6987 mL | 3.3974 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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