NMS-873

Protein target name:

VCP

Mechanism of action:

Allosteric Inhibitor

Recommended Concentration for use in cells:

Up to 5 uM

Probe Availability

MedChemExpress

Selleck Chemicals

Probe Information

Target and Probe Information

Target Details

Target class:

ATPase

Subclass:

AAA+

HUGO ID:

HGNC:12666

Entrez gene ID:

7415

UNIPROT ID:

P55072

Target alias:

p97; TERA; CDC48; FTDALS6

Probe Details

Chemical Probes Portal ID:

CPP2366

Probe alias:

cpd 6

PubChem CID:

71521142

ChEMBL ID:

CHEMBL2311578

SMILES string:

CC(C=C(OCC1=NN=C(SC2CCCC2)N1C3=CC=CN=C3)C=C4)=C4C5=CC=C(S(=O)(C)=O)C=C5

InChi Key:

UJGTUKMAJVCBIS-UHFFFAOYSA-N

Orthogonal probe:

CB-5083LC-1028

Physico-chemical properties

NMR:

1H-NMR (400 MHz, DMSO-d6): δ 8.75-8.71 (m, 2H), 8.03 (m, 1H), 7.95 (m, 2H), 7.63 (m, 1H), 7.57 (m, 2H), 7.14 (d, J = 8.30 Hz, 1H), 6.83-6.79 (m, 2H), 5.18 (s, 2H), 3.83 (m, 1H), 3.25 (s, 3H), 2.18 (s, 3H), 2.07 (m, 2H), 1.67-1.53 (m, 6H);

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

30 nM low ATP, 20 nM high ATP, 20 nM C522T

Potency assay:

ATPase Assay

Off target activity

Probe Selectivity in Vitro:

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

Outside target family: selective against HSP90 and 53 kinases analyzed

In cell validation

On target activity in cells

Potency in cells:

IC50

400 nM HCT116, 700 nM HeLa, 80-2000 nM

Potency assay (cells):

antiproliferative activity assay

Target engagement assay (cells):

Anti-proliferation assay; accumulation of poly-Ub proteins and stabilization of cyclin E and Mcl-1 in the low µM range; activation of the UPR, as assessed by increased GRP78, C/EBP homologous protein (CHOP) or its transcriptional target GADD34; induction of CHOP in low µM range.

Primary Reference

Reference (doi):

10.1038/nchembio.1313

Reference (PMID):

23892893

NMS-873

Probe Availability

Probe Information

Target Details

p97; TERA; CDC48; FTDALS6

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

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NMS-873

Probe Availability

Probe Information

Target Details

p97; TERA; CDC48; FTDALS6

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?