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DBeQ

Catalog No.
A8629
P97 ATPase inhibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$66.00
In stock
10mg
$90.00
In stock
50mg
$340.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

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Background

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.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt340.42
Cas No.177355-84-9
FormulaC22H20N4
Solubility≥16mg/mL in DMSO
Chemical Name2-N,4-N-dibenzylquinazoline-2,4-diamine
SDFDownload SDF
Canonical SMILESC1=CC=C(C=C1)CNC2=NC(=NC3=CC=CC=C32)NCC4=CC=CC=C4
Shipping ConditionEvaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.

Protocol

Cell experiment [1]:

Cell lines

HeLa cells, HEK293 cells

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.

Reacting condition

5 h

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.

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.

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.

Biological Activity

Description DBeQ is a selective, potent, reversible, and ATP-competitive inhibitor of p97 with an IC50 value of 1.5 μM.
Targets p97          
IC50 1.5 μM          

Quality Control

Chemical structure

DBeQ

Related Biological Data

DBeQ