JRF-12 DBeQ cas 177355-84-9

DBeQ, also known as JRF 12, is a selective, reversible, and ATP-competitive inhibitor of the ATPase p97 for treatment of cancer. DBeQ impairs both ubiquitin-dependent and autophagic protein clearance pathways. DBeQ was shown to inhibit the ATPase activity of Vps4 with an IC50 of about 11.5 μM. To a less degree, it also inhibits hyphal growth. DBeQ blocks multiple processes that have been shown by RNAi to depend on p97, including degradation of ubiquitin fusion degradation and endoplasmic reticulum-associated degradation pathway reporters, as well as autophagosome maturation. DBeQ also potently inhibits cancer cell growth and is more rapid than a proteasome inhibitor at mobilizing the executioner caspases-3 and -7.

[1]. Chou TF, et al.Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4834-9.

[2]. Zhang Y, et al. The AAA ATPase Vps4 Plays Important Roles in Candida albicans Hyphal Formation and is Inhibited by DBeQ. Mycopathologia. 2016 Jun;181(5-6):329-39.