DBeQ
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.
DBeQ是p97 ATP酶的选择性和可逆抑制剂(IC50 = 1.5 μM),能够迅速诱导caspase-3和caspase-9.
p97,亦称VCP(酵母中称Cdc48),是AAA家族的六聚体ATP酶,在膜融合后能使SNARE蛋白去组装[1].其参与同型膜融合\蛋白降解和膜结合转录因子的活化[2].p97是真核生物胞质中最丰富的蛋白之一,其隔离酶(segregase)功能与许多生物学过程相关,如内质网相关的降解(ERAD)\线粒体相关的降解\泛素融合降解\同型膜融合\细胞周期调控\自噬和转录因子调节[3].
DBeQ能阻断内质网相关降解(ERAD)受体的降解,也能阻断自噬体成熟,二者在癌症治疗中非常重要[4, 5].DBeQ 是ATP敏感性的,选择性靶向D1和D2结构域,ODD-Luc IC50 56 μM\Luc-ODC IC50 45 μM\UbG76VGFP IC50 2.3 μM,相比于其它噻唑啉类受p47的影响较小[6, 7].
参考文献：
1. Zhang, X. et al. "Structure of the AAA ATPase p97". Molecular cell 2000, 6 (6): 1473–84.
2. Madsen, L. et al. "New ATPase regulators--p97 goes to the PUB.". Int J Biochem Cell Biol 2009, 41 (12): 2380–8.
3. Eli Chapman. et al. “Inhibitors of the AAA+ Chaperone p97”. Molecules 2015, 20(2), 3027-3049.
4. Liu, Y. Et al. “VCP/p97,down-regulated by microRNA-129-5p, could regulate the progression of hepatocellular carcinoma”. PLoS One 2012, 7, e35800.
5. Lagu, M.N. et al. “Proteomic profiling of a mouse model for ovarian granulosa cell tumor identifies VCP as a highly sensitive serum tumor marker in several human cancers.” PLoS One 2012, 7, e42470.
6. Fang, C.J. et al. “Evaluating p97 inhibitor analogues for their domain selectivity and potency against the p97–p47 complex.” Chem. Med. Chem. 2014.
7. Chou, T.F. et al. “Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrated interaction between D1 and D2 ATPase domains.” J. Mol. Biol. 2014, 426, 2886–2899.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 340.42 |
| Cas No. | 177355-84-9 |
| Formula | C22H20N4 |
| Solubility | ≥16 mg/mL in DMSO; ≥2.24 mg/mL in H2O with gentle warming; ≥7.71 mg/mL in EtOH with ultrasonic |
| Chemical Name | 2-N,4-N-dibenzylquinazoline-2,4-diamine |
| SDF | Download SDF |
| Canonical SMILES | C1=CC=C(C=C1)CNC2=NC(=NC3=CC=CC=C32)NCC4=CC=CC=C4 |
| 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]: | |
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细胞系 |
HeLa细胞，HEK293细胞 |
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溶解方法 |
该化合物在DMSO中的溶解度大于16.0 mg/mL。若获取更高浓度的溶液，可在37℃下孵育10分钟，随后在超声波浴中摇匀。-20℃以下可储存数月。 |
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反应条件 |
5 h |
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应用 |
在HeLa细胞中，DBeQ阻断UbG76V-GFP、ODD-Luc和Luc-ODC降解，IC50分别为2.6 μM、56 μM和45 μM。DBEQ（10 μM）有效阻断HEK293细胞中TCRα-GFP的降解。在3小时内，DBeQ以剂量依赖性方式诱导CHOP。在Hela细胞中，DBeQ（15 μM）诱导细胞核中LC3-II的积累以及膜和胞质部分富集。在HeLa细胞中，DBeQ通过阻断LC3-II的自噬降解而不是引起自噬发挥作用。DBeQ（10 μM）快速促进了HeLa细胞中执行者caspase-3和-7的激活。与正常人胎儿肺成纤维细胞（MRC5）相比，DBeQ对多发性骨髓瘤（RPMI8226）细胞活性高5倍，对HeLa和Hek293细胞显示出中等敏感性。 |
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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。 |
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References: [1]. Chou T F, Brown S J, Minond D, et al. Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways[J]. Proceedings of the National Academy of Sciences, 2011, 108(12): 4834-4839. |
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| Description | DBeQ是高效\选择性\可逆和ATP竞争性p97抑制剂,IC50值为1.5 μM. | |||||
| 靶点 | p97 | |||||
| IC50 | 1.5 μM | |||||
质量控制和MSDS
- 批次:
化学结构
相关生物数据
