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  • 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. Check for \'https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C118287\' active clinical trials using this agent. (\'http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C118287\' NCI Thesaurus)
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