P97 is an AAA+ ATPase regulating endoplasmic reticulum–associated degradation. NMS-873 is a potent and selective p97 ATPase allosteric inhibitor with IC50 value of 30 nM, selective over all other AAA ATPases, HSP90 and kinases tested with IC50 >10 μM. NMS-873 exhibited antiproliferation on HCT116 cancer cell line cells with IC50 value of 0.4μM. It induced clear, dose-dependent accumulation of poly-Ub proteins and stabilization of cyclin E and Mcl-1 at concentration at 0.5, 2.5 and 5μM in HCT116 cells at 8h and 24h post treatment[1]. NMS-873 also showed potent HCMV antiviral effect with potential as a novel host targeting therapeutic for HCMV infection. Pretreatment with NMS-873 at 1μM clearly inhibited the production of infectious virus in human primary fibroblast cells infected at high multiplicity of infection with HCMV[2]
作用机制
NMS-873 is a non–ATP-competitive p97 inhibitor with a new allosteric mechanism.[1]
NMS-873 细胞研究
细胞系
浓度
检测类型
检测时间
活性说明
数据源
HCT116 cells
Cytotoxic assay
72 h
Cytotoxicity against human HCT116 cells after 72 hrs by luciferase reporter gene assay, IC50=0.38 μM
71521142
Hi5 cells
Function assay
20 mins
Inhibition of human recombinant His-GST tagged VCP expressed in baculovirus infected Hi5 cells assessed as ADP formation incubated for 20 mins proir to substrate addition measured after 90 mins by NADH coupled assay, IC50=0.024 μM
Cytotoxicity against human HCT116 cells after 72 hrs by luciferase reporter gene assay, IC50=0.38 μM
71521142
Hi5 cells
Function assay
20 mins
Inhibition of human recombinant His-GST tagged VCP expressed in baculovirus infected Hi5 cells assessed as ADP formation incubated for 20 mins proir to substrate addition measured after 90 mins by NADH coupled assay, IC50=0.024 μM
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