NMS-873

Allosteric Inhibitor of VCP

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe NMS-873 is in the process of SERP review.

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Information

Allosteric Inhibitor

Probe Availability:

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 ...

DOI Reference: 10.1038/nchembio.1313

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

Selective (IC50 >10 μM) against all of the AAA ATPases

Outside target family: selective against HSP90 and 53 kinases analyzed

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

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

SERP Comments:

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 )