Allosteric Inhibitor of VCP



Protein target names: VCP

Mechanism of action: Allosteric Inhibitor

In Vitro Validations

Uniprot ID: P55072
Target Class: ATPase
Target SubClass: AAA+
Potency: IC50
Potency Value: 30 nM low ATP; 20 nM high ATP; 20 nM C522T
Potency Assay: ATPase Assay
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Transitional endoplasmic reticulum ATPase, TERA_HU ...

In Cell Validations

In Vivo Data

No in Vivo Validations

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SERP ratings and comments

SERP Ratings

In Cell Rating


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.

(last updated: 19 Sept 2021 )

SERP Ratings

In Cell Rating


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).

(last updated: 28 Sept 2021 )