1. Cell Cycle/DNA Damage
  2. p97

NMS-873 

Cat. No.: HY-15713 Purity: 99.93%
Data Sheet SDS 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

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Free Sample (0.5-1 mg)   Apply now  
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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    NMS-873 purchased from MCE. Usage Cited in: J Cell Mol Med. 2016 Jan;20(1):58-70.

    Efficient TNF-induced degradation of IκBα and concomitant liberation of RelA requires functional p97/VCP. Cells stimulated with TNF (10 ng/mL) for the indicated times after either pretreatment with p97/VCP inhibitor NMS-873 (2.5 μM, NMS3) for 10 min. or inhibitor treatment (2.5 μM) from 15 min. after stimulation in either the presence (NMS1) or the absence (NMS2) of pan-caspase inhibitor ZVAD-fmk (10 μM), are subjected to subcellular fractionation. LMB (10 ng/mL)

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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 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
    Please refer to the solubility information to select the appropriate solvent.
    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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    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

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Purity: 99.93%

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    Product Name:
    NMS-873
    Cat. No.:
    HY-15713
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