DBeQ
(Synonyms: JRF 12) 目录号 : GC10824
A selective inhibitor of the ATPase p97
Cas No.:177355-84-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
HeLa cells, HEK293 cells |
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Preparation method |
The solubility of this compound in DMSO is > 16.0 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
5 h |
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Applications |
In HeLa cells, DBeQ blocked UbG76V-GFP, ODD-Luc and Luc-ODC degradation with IC50 of 2.6 μM, 56 μM and 45 μM. DBeQ (10 μM) potently blocked degradation of TCRα-GFP in HEK293 cells. DBeQ dose-dependently induced CHOP within 3 hours. DBeQ (15 μM) induced a strong accumulation of LC3-II in the nucleus plus membrane-enriched and cytosolic fractions in Hela cells. DBeQ functioned by blocking autophagic degradation of LC3-II instead of inducing autophagy in HeLa cells. DBeQ (10 μM) rapidly promoted activation of the “executioner” caspases-3 and -7 in HeLa cells. DBeQ was five-fold more active against multiple myeloma (RPMI8226) cells than normal human fetal lung fibroblasts (MRC5), with HeLa and Hek293 cells showing intermediate sensitivities. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
DBeQ is a selective and reversible inhibitor of p97 ATPase (IC50 = 1.5 μM) which induces caspase-3 and caspase-7 rapidly.
p97 knows also as VCP ( Cdc48 in yeast) is a hexameric ATPase of the AAA family which disassembles SNARE proteins after membrane fusion.[1] It is involved in a fusion of homotypic membranes, protein degradation, and activation of membrane-bound transcription factors.[2] p97 is one of the most abundant proteins in the eukaryotic cytosol and its segregase function has been linked to a large number of biological processes including endoplasmic reticulum-associated degradation(ERAD), mitochondrial associated degradation, ubiquitin fusion degradation, homotypic membrane fusion, cell cycle regulation, autophagy and transcription factor regulation.[3]
DBeQ can block the degradation of endoplasmic reticulum-associated degradation (ERAD) reporters and also block autophagosome maturation,all of which are proven to be important in cancer therapy.[4,5] DBeQ is ATP-sensitive and selectively target D1and D2 domain with ODD-Luc IC50 56 μM, Luc-ODC IC50 45 μM,UbG76VGFP IC50 2.3 μM, much less affected by the presence of p47 than the other quinazolines.[6,7]
References:
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. Laguë, 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.
| Cas No. | 177355-84-9 | SDF | |
| 别名 | JRF 12 | ||
| 化学名 | 2-N,4-N-dibenzylquinazoline-2,4-diamine | ||
| Canonical SMILES | C1=CC=C(C=C1)CNC2=NC(=NC3=CC=CC=C32)NCC4=CC=CC=C4 | ||
| 分子式 | C22H20N4 | 分子量 | 340.42 |
| 溶解度 | ≥ 16mg/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 | 2.9375 mL | 14.6877 mL | 29.3755 mL |
| 5 mM | 0.5875 mL | 2.9375 mL | 5.8751 mL |
| 10 mM | 0.2938 mL | 1.4688 mL | 2.9375 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。