VCP/p97 is an ATPase involved in the regulation of protein trafficking and degradation that has been increasingly linked to cancer. The lack of potent and specific inhibitors has so far limited the assessment of VCP/p97 as a target for cancer therapy.
In a paper just published in Nature Chemical Biology, Nerviano Medical Sciences and Genentech scientists highlight the potential of VCP/p97 as an anticancer drug target whose function can be modulated by small molecule compounds via different biochemical mechanisms. These include covalent modification of the amino acid cysteine residing in the enzyme “active site”, and a new allosteric mechanism of inhibition. Exploration of a class of “allosteric type” inhibitors led to the identification of NMS-873, the most potent and specific VCP/p97 inhibitor reported to date.
See the Advance Online Publication: Magnaghi, P., et al. Covalent and allosteric inhibitors of the ATPase VCP/p97 induce cancer cell death. Nature Chemical Biology (2013).