MHY1485
目录号 : GC13790
MHY1485 是一种有效的 mTOR 激活剂，可抑制自噬以及自噬体与溶酶体之间的融合。
Cas No.:326914-06-1
Sample solution is provided at 25 µL, 10mM.
MHY1485 is a potent activator of mTOR, which inhibits autophagy and the fusion between autophagosomes and lysosomes[1].
MHY1485 has an inhibitory effect on the autophagic process by inhibition of fusion between autophagosomes and lysosomes leading to the accumulation of LC3II protein and enlarged autophagosomes. MHY1485 also induces mTOR activity, providing a possibility for another regulatory mechanism of autophagy by the MHY compound[2]. In the activation of mTOR in HCC cells MHY1485, gdc inhibited the autophagy activity induced by gdc by upregulating the expression of p-mTOR and downregulating the expression of LC3 and p62 [3]. MHY1485 inhibits UV-induced skin cell damages via activating mTOR-Nrf2 signaling[6].MHY1485 treatment inhibited growth and colony formation in both cell lines under irradiation and no-irradiation conditions, results that were not fully consistent with MHY1485's known role in activating mTOR signaling. Combined treatment with MHY1485 and radiation significantly increased apoptosis and senescence in tumor cells in association with oxidative stress, ER stress and p21 stabilization, compared to radiation treatment alone[5].
MHY1485 (an agonist of mTOR) significantly suppressed autophagy signaling by activating mTOR. The expression of hypoxia-inducible factor 1-alpha (HIF-1α) was increased after FSH treatment. Blocking hypoxia-inducible factor 1-alpha attenuated autophagy signaling. [4]. SN potentiated the motor ability in PD mice, promoted the survival of dopaminergic neurons, increased the protein expression level of Beclin1, LC3-II/LC3-I ratio and LC3B-positive neurons, lowered the protein expression level of p62 and inactivated PI3K/AKT/mTOR pathway in the substantia nigra tissue of mouse brains. Moreover, MHY1485 reversed the above effects of SN on PD mice via reactivating PI3K/AKT/mTOR pathway[7].
References:
[1]: Yang B, Zhou Y,et,al. ω-6 Polyunsaturated fatty acids (linoleic acid) activate both autophagy and antioxidation in a synergistic feedback loop via TOR-dependent and TOR-independent signaling pathways. Cell Death Dis. 2020 Jul 30;11(7):607. doi: 10.1038/s41419-020-02750-0. PMID: 32732901; PMCID: PMC7393504.
[2]: Choi YJ, Park YJ, et,al. Inhibitory effect of mTOR activator MHY1485 on autophagy: suppression of lysosomal fusion. PLoS One. 2012;7(8):e43418. doi: 10.1371/journal.pone.0043418. Epub 2012 Aug 22. Erratum in: PLoS One. 2013;8(1). doi:10.1371/annotation/e3163ad5-f3d8-4a21-b3e1-f2033a76f9db. PMID: 22927967; PMCID: PMC3425474.
[3]: Gao L, Lv G, et,al. Glycochenodeoxycholate promotes hepatocellular carcinoma invasion and migration by AMPK/mTOR dependent autophagy activation. Cancer Lett. 2019 Jul 10;454:215-223. doi: 10.1016/j.canlet.2019.04.009. Epub 2019 Apr 11. PMID: 30980867.
[4]: Zhou J, Yao W, et,al. Administration of follicle-stimulating hormone induces autophagy via upregulation of HIF-1α in mouse granulosa cells. Cell Death Dis. 2017 Aug 17;8(8):e3001. doi: 10.1038/cddis.2017.371. PMID: 28817115; PMCID: PMC5596559.
[5]: Sun L, Morikawa K, et,al. MHY1485 enhances X-irradiation-induced apoptosis and senescence in tumor cells. J Radiat Res. 2021 Sep 13;62(5):782-792. doi: 10.1093/jrr/rrab057. PMID: 34265852; PMCID: PMC8438247.
[6]: Yang B, Xu QY, et,al. MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling. Oncotarget. 2017 Feb 21;8(8):12775-12783. doi: 10.18632/oncotarget.14299. PMID: 28061443; PMCID: PMC5355053.
[7]: Bao X, He Y, et,al. Sinomenine exerts a neuroprotective effect on PD mouse model through inhibiting PI3K/AKT/mTOR pathway to enhance autophagy. Int J Neurosci. 2022 Jul 18:1-9. doi: 10.1080/00207454.2022.2100780. Epub ahead of print. PMID: 35815397.
MHY1485 是一种有效的 mTOR 激活剂，可抑制自噬以及自噬体与溶酶体之间的融合[1]。
MHY1485 通过抑制自噬体和溶酶体之间的融合导致 LC3II 蛋白的积累和扩大的自噬体，从而对自噬过程产生抑制作用。 MHY1485 还诱导 mTOR 活性，为 MHY 化合物[2] 的自噬的另一种调节机制提供了可能性。在HCC细胞MHY1485中mTOR的激活中，gdc通过上调p-mTOR的表达，下调LC3和p62的表达来抑制gdc诱导的自噬活性[3]。 MHY1485 通过激活 mTOR-Nrf2 信号抑制紫外线诱导的皮肤细胞损伤[6]。MHY1485 处理在辐照和非辐照条件下抑制两种细胞系的生长和集落形成，结果不完全一致MHY1485 在激活 mTOR 信号传导中的已知作用。与单独放疗相比，MHY1485 和放疗联合治疗显着增加了与氧化应激、ER 应激和 p21 稳定相关的肿瘤细胞凋亡和衰老[5]。
MHY1485（mTOR 的激动剂）通过激活 mTOR 显着抑制自噬信号。 FSH 处理后缺氧诱导因子 1-α (HIF-1α) 的表达增加。阻断缺氧诱导因子 1-alpha 可减弱自噬信号。 [4]。 SN 增强 PD 小鼠的运动能力，促进多巴胺能神经元的存活，增加 Beclin1、LC3-II/LC3-I 比率和 LC3B 阳性神经元的蛋白表达水平，降低 p62 的蛋白表达水平并使 PI3K/AKT 失活/mTOR 通路在小鼠大脑的黑质组织中。此外，MHY1485通过重新激活PI3K/AKT/mTOR信号通路逆转了SN对PD小鼠的上述影响[7]。
| Cell experiment [1]: | |
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Cell lines |
Ac2F cell |
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Preparation Method |
Ac2F cells were treated with different concentrations of MHY1485 and 5 µM rapamycin as a positive control for 6 hours. |
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Reaction Conditions |
0-2uM MHY1485 for 6 hours |
|
Applications |
MHY1485 has an inhibitory effect on the autophagic process by inhibition of fusion between autophagosomes and lysosomes leading to the accumulation of LC3II protein and enlarged autophagosomes. MHY1485 also induces mTOR activity, providing a possibility for another regulatory mechanism of autophagy by the MHY compound. |
| Animal experiment [2]: | |
|
Animal models |
3-4 week old female ICR mice |
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Preparation Method |
To induce MGC autophagy, mice were injected i.p. with FSH on four successive occasions at 12 h intervals.For activator and inhibitor experiments, MHY1485 (10 mg/kg, 2 days) and chloroquine obtained from Sigma were injected before FSH administration. |
|
Dosage form |
10 mg/kg MHY1485 for 2 days(intraperitoneal injection) |
|
Applications |
MHY1485 (an agonist of mTOR) significantly suppressed autophagy signaling by activating mTOR. The expression of hypoxia-inducible factor 1-alpha (HIF-1α) was increased after FSH treatment. Blocking hypoxia-inducible factor 1-alpha attenuated autophagy signaling. |
|
References: [1]: Choi YJ, Park YJ, et,al.Inhibitory effect of mTOR activator MHY1485 on autophagy: suppression of lysosomal fusion. PLoS One. 2012;7(8):e43418. doi: 10.1371/journal.pone.0043418. Epub 2012 Aug 22. Erratum in: PLoS One. 2013;8(1). doi:10.1371/annotation/e3163ad5-f3d8-4a21-b3e1-f2033a76f9db. PMID: 22927967; PMCID: PMC3425474. |
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| Cas No. | 326914-06-1 | SDF | |
| 化学名 | 4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine | ||
| Canonical SMILES | [O-][N+](C1=CC=C(NC2=NC(N3CCOCC3)=NC(N4CCOCC4)=N2)C=C1)=O | ||
| 分子式 | C17H21N7O4 | 分子量 | 387.39 |
| 溶解度 | ≥ 19.35mg/mL in DMSO | 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 | 2.5814 mL | 12.9069 mL | 25.8138 mL |
| 5 mM | 0.5163 mL | 2.5814 mL | 5.1628 mL |
| 10 mM | 0.2581 mL | 1.2907 mL | 2.5814 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
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Related Biological Data
The mTORC1 overactivation and fundus changes. Fundus photographs and optical coherence tomographic images of the eyes of guinea pigs that underwent 3 months of binocular NLIAE. The right eyes received weekly intravitreal injections of 5μg of MHY1485. At week 12, images were taken of eyes of the negative control group (a, b), eyes undergoing NLIAE.
The right eyes received weekly intravitreal injections of 5μg of MHY1485 (GLPBIO, USA).
Invest Ophth Vis Sci, 2023, 64(10): 24-24. PMID: 37466949 IF: 4.3997 -
Related Biological Data
CYB561 KD inhibits the Akt/mTOR signaling pathways. I, Quantitative results of the EdU assay demonstrating that MHY1485 reverses the inhibitory effect of CYB561 KD on cell proliferation.
The proportion of EdU positive cells in both control and CYB561 KD cells were increased after MHY1485 (5μM, 24h) (GLPBIO, USA) treatment.
Experimental Cell Research, 2023: 113760. PMID: 37634562 IF: 3.7001