NCIt definition : An orally bioavailable inhibitor of valosin-containing protein (VCP) p97, with potential
antineoplastic activity. Upon oral administration, CB-5083 specifically binds to and
inhibits the activity of p97. This prevents ubiquitin-dependent protein degradation
and causes cellular accumulation of poly-ubiquitinated proteins. The inhibition of
endoplasmic reticulum (ER)-associated protein degradation activates the ER-dependent
stress response pathway, and leads to both an induction of apoptosis and inhibition
of cell proliferation in susceptible tumor cells. p97, a type II AAA ATPase, plays
a key role in cellular protein homeostasis. Its overexpression in many tumor cell
types is associated with increased tumor cell proliferation and survival.;
Semantic type(s)