NMS-873

Limited selectivity data (AAA ATPase, HSP90 and 53 kinases) and no wide ligand profiling data. The high lipophilicity of the compound is a concern regarding off-target selectivity. No data regarding in-cell occupancy of VCP and its relation to the biomarkers or antiproliferation phenotype that might describe the shift in potency from 30 nM in vitro.

In vitro selectivity data within the target family (all AAA ATPases) and limited selectivity outside the target family (HSP90 and 53 kinases) are presented. However, an in-cell target engagement study using NMS-873 is lacking. Recent publications call for caution regarding potential polypharmacology and off-target effects of this compound: broad antiviral activity against influenza A and B viruses (Zhang et al) and dual inhibition of mitochondrial oxidative phosphorylation (Bouwer et al) have been reported. Zhang et al. Eur J Pharm Sci 2019, 133, 86–94(https://doi.org/10.1016/j.ejps.2019.03.020). Bouwer et al. Biochimie 2021, 185, 33–42. (https://doi.org/10.1016/j.biochi.2021.03.004).