SBI-0206965
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.
SBI-0206965是一种新型的自噬启动激酶ULK1抑制剂。
ULK1（UNC-51样自噬激活激酶1）是参与饥饿中自噬的一种丝氨酸/苏氨酸蛋白激酶。该物质是AMPK的调控子，是mTORC1的下游效应器和负调控因子。该物质在神经元分化中扮演重要角色。[1]
在A549细胞中，5 mM的SBI-0206965可强效抑制AZD8055诱导的自噬效应。在SBI-0206965处理的MEF中，氨基酸剥夺后18小时，6965个处理的细胞中42%表现出7-AAD和AnnexinV（末期凋亡）。SBI-02066965在人类U87MG胶质母细胞瘤和小鼠肺癌肿瘤细胞的营养饥饿阶段中也可促进细胞凋亡。此外，5 mM的SBI-0206965与AZD8055共同使用可引起23%的细胞凋亡，而AZD8055缺乏时为10%，仅有AZD8055时为7%。与AZD8055相似，雷帕霉素和INK128在A549细胞中均具有温和的自身凋亡响应，但与SBI-0206965联合使用能够显著提高凋亡响应。[1]
参考文献：
1. Egan DF, Chun MG, Vamos M et al. Small Molecule Inhibition of the Autophagy Kinase ULK1 and Identification of ULK1 Substrates. Mol Cell. 2015 Jul 16;59(2):285-97.
- 1. Jonas Sundermeyer. "Effekte einer pharmakologischen Inhibition der ULK1-Kinase auf die akute axonalen Degeneration in vivo." Göttingen 2022.
- 2. Mathieu Paquette, Leeanna El-Houjeiri, et al. "AMPK-dependent phosphorylation is required for transcriptional activation of TFEB and TFE3." Autophagy. 2021 Dec;17(12):3957-3975. PMID: 33734022
- 3. Yoon-Jin Kim, Qingyao Kong, et al. "An autophagy-related protein Becn2 regulates cocaine reward behaviors in the dopaminergic system." Sci Adv. 2021 Feb 19;7(8):eabc8310. PMID: 33608268
- 4. Vahsen BF, Ribas VT, et al. "Inhibition of the autophagic protein ULK1 attenuates axonal degeneration in vitro and in vivo, enhances translation, and modulates splicing." Cell Death Differ. 2020;10.1038/s41418-020-0543-y. PMID: 32341448
- 5. Dite TA, Langendorf CG, et al. "AMP-activated protein kinase selectively inhibited by the type II inhibitor SBI-0206965." J Biol Chem. 2018 Jun 8;293(23):8874-8885. PMID: 29695504
- 6. Dite TA, Ling NXY, et al. "The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs." Nat Commun. 2017 Sep 18;8(1):571. PMID: 28924239
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 489.32 |
| Cas No. | 1884220-36-3 |
| Formula | C21H21BrN4O5 |
| Solubility | ≥24.47 mg/mL in DMSO; insoluble in H2O; ≥5 mg/mL in EtOH with ultrasonic |
| Chemical Name | (Z)-2-((5-bromo-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)oxy)-N-methylbenzimidic acid |
| SDF | Download SDF |
| Canonical SMILES | C/N=C(O)/C1=CC=CC=C1OC2=NC(NC3=CC(OC)=C(OC)C(OC)=C3)=NC=C2Br |
| 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 |
转染WT或KI Myc标记的ULK1以及WT Vps34的HEK293T细胞 |
|
制备方法 |
在DMSO中的溶解度大于24.5 mg/mL。若配制更高浓度的溶液，一般步骤如下：请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。 |
|
反应条件 |
1、10和50 μM；1小时 |
|
实验结果 |
在转染WT或KI Myc标记的ULK1以及WT Vps34的HEK293T细胞中，SBI-0206965在约5 μM的剂量下抑制过表达Vps34的Ser249磷酸化。据发现，在HEK293T细胞中，SBI-0206965也对Beclin1 Ser15显示相当的磷酸化抑制作用。 |
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References: [1]. Egan DF, Chun MG, Vamos M et al. Small Molecule Inhibition of the Autophagy Kinase ULK1 and Identification of ULK1 Substrates. Mol Cell. 2015 Jul 16;59(2):285-97. |
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质量控制和MSDS
- 批次:
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