NMS-873

NMS-873 is a **potent allosteric and specific inhibitor** of the **AAA ATPase VCP/p97 (valosin-containing protein)**, a crucial regulator of protein homeostasis and the ubiquitin-proteasome system. Identified through high-throughput screening, NMS-873 acts with an IC50 in the low nanomolar range (about 30 nM in biochemical assays)[7][8]. It exerts **anti-proliferative effects** across a range of tumor cell lines, with reported IC50 values from 0.08 μM to 2 μM. In addition to its canonical role as a p97 inhibitor, NMS-873 has been found to **inhibits mitochondrial Complex I and ATP synthase**, resulting in suppressed oxidative phosphorylation and increased cellular reliance on glycolysis[1][2]. These mitochondrial effects are observed at higher concentrations and **partially independent of p97 inhibition**. NMS-873 has also demonstrated **broad-spectrum antiviral activity** in cell models, notably against influenza A and B viruses, by inhibiting the intermediate stage of viral replication[4].