1. Cell Cycle/DNA Damage
  2. p97

NMS-873 (Synonyms: NMS873; NMS 873)

Cat. No.: HY-15713 Purity: 98.44%
Handling Instructions

NMS-873 is a potent, selective allosteric VCP/p97 inhibitor with IC50 value of 20 nM (Wild Type, 1 mM ATP).

For research use only. We do not sell to patients.
NMS-873 Chemical Structure

NMS-873 Chemical Structure

CAS No. : 1418013-75-8

Size Price Stock Quantity
10 mM * 1 mL in DMSO $80 In-stock
5 mg $70 In-stock
10 mg $120 In-stock
50 mg $450 In-stock
100 mg $765 In-stock
200 mg   Get quote  
500 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

NMS-873 is a potent, selective allosteric VCP/p97 inhibitor with IC50 value of 20 nM (Wild Type, 1 mM ATP).

IC50 & Target

IC50: 20 nM (Wild Type VCP, ATP)

In Vitro

NMS-873 has antiproliferative effect on a panel of tumor cell lines with IC50 values in the range of 0.08 μM to 2 μM. For HCT116 and HeLa cells, the IC50 values are 0.4 μM and 0.7 μM, respectively. NMS-873 reduces VCP sensitivity to trypsin digestion, preventing degradation of the linker-D2 domain. NMS-873 induces clear, dose-dependent accumulation of poly-Ub proteins and stabilization of cyclin E and Mcl-1 at doses consistent with its antiproliferative IC50 value[1]

References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 1.9206 mL 9.6030 mL 19.2060 mL
5 mM 0.3841 mL 1.9206 mL 3.8412 mL
10 mM 0.1921 mL 0.9603 mL 1.9206 mL
Kinase Assay
[1]

The ATPase activity and the kinetic parameters of recombinant wild-type VCP and its mutants are evaluated by monitoring ADP formation in the reaction, using a modified NADH-coupled assay46. As ADP and NADH are ATP-competitive inhibitors of VCP ATPase activity, the standard protocol for the NADH-coupled assay is modified into a two-step procedure. In the first part, an ATP-regenerating system (40 U/mL pyruvate kinase and 3 mM phosphoenolpyruvate) recycles the ADP produced by VCP activity, keeps the substrate concentration constant (thus preventing product inhibition) and accumulates a stoichiometric amount of pyruvate. In the second part, the VCP enzymatic reaction is quenched with 30 mM EDTA and 250 μM NADH and stoichiometrically oxidized by 40 U/mL lactic dehydrogenase to reduce accumulated pyruvate. The decrease of NADH concentration is measured at 340 nm using a Tecan Safire 2 reader plate. The assay is performed in 96- or 384-well UV platesin a reaction buffer with 50 mM Hepes, pH 7.5, 0.2 mg/mL BSA, 10 mM MgCl2 and 2 mM DTT.

Cell Assay
[1]

Cells are seeded at 1,600 cells per well in 384-well white clear-bottom plates. Twenty-four hours after seeding, cells are treated with the compounds (eight dilution points, in duplicate, for each compound) and incubated for an additional 72 h at 37°C under a 5% CO2 atmosphere. Cells are then lysed, and the ATP content in each well is determined using a thermostable firefly luciferase-based assay from Promega as a measure of cell viability. IC50 values are calculated using the percentage of growth of treated cells versus the untreated control.

References
M.Wt

520.67

Formula

C₂₇H₂₈N₄O₃S₂

CAS No.

1418013-75-8

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: 20.5 mg/mL

Purity: 98.44%

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NMS-873
Cat. No.:
HY-15713
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