P97 ATPase, which is also known as VCP (valosin-containing protein) or TERA (translational endoplasmic reticulum ATPase), has various substrates,such as LC3,HIF1A, CYP3a. It is involved in autophagy, ERAD pathway etc.. DBeQ can inhibit p97 selectively and potently in a reversible and ATP-competitive manner. Different from the conventional proteasome inhibitors, DBeQ affects both the UPS and autophagic protein degradation pathways. DBeQ can also rapidly activate caspases 3/7 and induce cell death, which target p97 in cancer therapy[1].
作用机制
DBeQ binds to the active site of the D2 domain and inhibits p97 in an ATP-competition manner.[1]
DBeQ 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Escherichia coli DnaK
100μM
Binds to DnaK without affecting its ATPase activity
J Biol Chem. 2021 Jan-Jun;296:100079.
Escherichia coli ClpB
45μM
Inhibits the ATPase activity of ClpB
J Biol Chem. 2021 Jan-Jun;296:100079.
OVCAR8
3 μM
48 h
To study the synergistic effect of DBeQ and Salubrinal on OVCAR8 cells, results showed that the combination enhances cytotoxicity.
Mol Oncol. 2016 Dec;10(10):1559-1574.
OVCAR5
4.5 ± 1.3 μM
72 h
To evaluate the cytotoxic effect of DBeQ on OVCAR5 cells, results showed that DBeQ is cytotoxic to OVCAR5 cells.
Mol Oncol. 2016 Dec;10(10):1559-1574.
SKOV3
10 μM
48 h
To study the apoptotic effect of DBeQ on SKOV3 cells, results showed that DBeQ induces apoptosis through caspase-3 activation.
Mol Oncol. 2016 Dec;10(10):1559-1574.
OVCAR10
2.5 ± 0.62 μM
72 h
To evaluate the cytotoxic effect of DBeQ on ovarian cancer cell lines, results showed that DBeQ is cytotoxic to ovarian cancer cells.
Mol Oncol. 2016 Dec;10(10):1559-1574.
RPMI8226 cells
10 μM
48 h
Evaluate the inhibitory effect of DBeQ on cancer cell growth, observed significant growth inhibition
Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4834-9.
Hek293 cells
10 μM
2 h
Evaluate the effect of DBeQ on the ERAD pathway, observed accumulation of TCRα-GFP
Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4834-9.
HeLa cells
10 μM
3 h
Evaluate the effect of DBeQ on the autophagy pathway, observed accumulation of LC3-II
Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4834-9.
DBeQ 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
LPS-induced lung damage model
Intraperitoneal injection
20 mg/kg
Once daily for 7 days
DBeQ treatment significantly decreased the generation of p52
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