The p97 AAA (ATPase associated with diverse cellular activities) is a 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. Valosin-containing protein (VCP), also known as VCP/p97, is an AAA ATPase family member that serves as an integral component of the ubiquitin fusion degradation pathway and is overexpressed in many tumor types. NMS-873 is a VCP inhibitor (IC50 = 24 nM) that demonstrates potent selectivity for VCP/p97 compared to a panel of other AAA ATPases, Hsp90, and 53 additional analyzed kinases (IC50s >10 μM). It has been shown to inhibit the proliferation of HCT116 cancer cells with an IC50 value of 380 nM.
