Description
DBeQ (177355-84-9) is a potent, selective and reversible inhibitor of the AAA-ATPase p97 (ATPase associated with diverse cellular activities). Ki=3.2 μM. DBeQ blocks ubiquitin-dependent protein clearance pathways. Cell permeable.
Uses
The ATPase p97 is an ubiquitin-selective chaperone known to play a critical role in the degradation of misfolded membrane and secretory proteins and has been linked to various cellular processes that require unfolding and disassembly of protein complexes. DBeQ is a selective, reversible, and ATP-competitive inhibitor of the ATPase p97 (Ki = 3.2 μM; IC50 = 1.5 μM). It does not exhibit activity when tested against a panel 170 protein kinases at concentrations as high as 15 μM. At 10 μM it blocks endoplasmic reticulum-associated degradation, impairing the autophagy pathway and promoting the activation of caspase-3 and -7 in cancer cells.[Cayman Chemical]
Uses
HeLa cells were treated with DBeQ and the effects on
in vivo ubiquitination and protein dislocation were studied by live cell imaging.
Biochem/physiol Actions
DBeQ is a potent and specific inhibitor of ATPase p97, an integral component of the ubiquitin-fusion degradation (UFD) pathway. DBeQ inhibits the degradation of ubiquitinated proteins, the endoplasmic reticulum-associated degradation pathway, and autophagosome maturation. The compound also potently inhibits cellular proliferation and induces caspase 3/7 activity and apoptosis.
References
[1] TSUI-FEN CHOU. Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2011: 4834-4839. DOI:
10.1073/pnas.1015312108
