NMS-873 (NMS873) is a potent, specific, cell-permeable, non-ATP competitive, allosteric inhibitor of VCP/p97 ATPase with IC50 of 30 nM.
NMS-873 displays high selectivity over all other AAA ATPases, HSP90 and kinases tested at 10 uM.
NMS-873 activates the unfolded protein response (UPR), interferes with autophagy and induced cancer cell death.
p97 A530T mutant is sufficient to overcome the cytotoxicity of NMS-873 and alleviates p97 composition changes caused by the molecule but not other p97 inhibitors.
NMS-873 also is a potent HCMV antiviral with potential for HCMV infection via host VCP/p97 inhibition.
NMS-873 exhibits antiproliferative activity in cancer cells in vitro (IC50= 400 and 700 nM for HCT116 and HeLa cells respectively).
