1. Metabolic Enzyme/Protease Anti-infection
  2. Proteasome Bacterial HIV
  3. ONX-0914

ONX-0914 (PR-957) is a selective inhibitor of low-molecular mass polypeptide-7 (LMP7), the chymotrypsin-like subunit of the immunoproteasome. ONX-0914 blocks cytokine production and attenuates progression of experimental arthritis. ONX-0914 is a noncompetitive irreversible inhibitor of the mycobacterial proteasome (Ki=5.2 μM). ONX-0914 reactivates latent HIV-1 through p-TEFb activation mediated by HSF-1.

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CAS 番号 : 960374-59-8

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10 mM * 1 mL in DMSO
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カスタマーレビュー

Based on 24 publication(s) in Google Scholar

Other Forms of ONX-0914:

Top Publications Citing Use of Products

    ONX-0914 purchased from MedChemExpress. Usage Cited in: Biochem Pharmacol. 2018 Oct:156:511-523.  [Abstract]

    The accumulated poly-ubiquitinated protein is detected by Western blotting after J-Lat 10.6 cells are treated with DMSO, PR-957 (100 nM), PR-957 (150 nM) or MG132 (500 nM) for 48 h.

    ONX-0914 purchased from MedChemExpress. Usage Cited in: Biochem Pharmacol. 2018 Oct:156:511-523.  [Abstract]

    Western blot detection of the p-TEFb component CDK9, Cyclin T1 and CDK9 phosphorylation on Thr186, as well as its downstream RNA poly II CTD and phosphate CTD after J-Lat 10.6 cells are treated with PR-957 in dose-dependent manner.

    ONX-0914 purchased from MedChemExpress. Usage Cited in: Biochem Pharmacol. 2018 Oct:156:511-523.  [Abstract]

    J-Lat 10.6 cells are treated with DMSO, PR-957 (150 nM) or Carfilzomib (40 nM) alone with or without the HSF1 inhibitor KRIBB11 (1.25 µM) for 48 h. Then the cells are lysed, and Ser320 phosphorylated HSF1, total HSF1 and p24 are detected by Western blot with the corresponding antibodies.

    HIV アイソフォーム固有の製品をすべて表示:

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    製品説明

    ONX-0914 (PR-957) is a selective inhibitor of low-molecular mass polypeptide-7 (LMP7), the chymotrypsin-like subunit of the immunoproteasome. ONX-0914 blocks cytokine production and attenuates progression of experimental arthritis. ONX-0914 is a noncompetitive irreversible inhibitor of the mycobacterial proteasome (Ki=5.2 μM). ONX-0914 reactivates latent HIV-1 through p-TEFb activation mediated by HSF-1[1][2][3].

    IC50 & Target

    HIV-1

     

    Cellular Effect
    Cell Line Type Value Description References
    Caco-2 EC50
    1.3 μM
    Compound: ONX-0914
    Cytotoxicity against human Caco2 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    Cytotoxicity against human Caco2 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    [PMID: 29339252]
    Fibroblast EC50
    0.16 μM
    Compound: ONX-0914
    Cytotoxicity against human fibroblasts assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    Cytotoxicity against human fibroblasts assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    [PMID: 29339252]
    HCT-116 EC50
    0.11 μM
    Compound: ONX-0914
    Cytotoxicity against human HCT116 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    Cytotoxicity against human HCT116 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    [PMID: 29339252]
    Huh-7 EC50
    0.39 μM
    Compound: ONX-0914
    Cytotoxicity against human HuH7 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    Cytotoxicity against human HuH7 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    [PMID: 29339252]
    MCF7 EC50
    0.26 μM
    Compound: ONX-0914
    Cytotoxicity against human MCF7 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    Cytotoxicity against human MCF7 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    [PMID: 29339252]
    MDA-MB-231 EC50
    0.27 μM
    Compound: ONX-0914
    Cytotoxicity against human MDA-MB-231 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    Cytotoxicity against human MDA-MB-231 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    [PMID: 29339252]
    MM1.S IC50
    0.24 μM
    Compound: 4; ONX-091
    Antiproliferative activity against human MM1.S cells assessed as inhibition of cell proliferation after 72 hrs by MTS assay
    Antiproliferative activity against human MM1.S cells assessed as inhibition of cell proliferation after 72 hrs by MTS assay
    [PMID: 34087498]
    NCI-H727 EC50
    0.3 μM
    Compound: ONX-0914
    Cytotoxicity against human NCI-H727 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    Cytotoxicity against human NCI-H727 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    [PMID: 29339252]
    PBMC IC50
    0.12 μM
    Compound: 3; ONX 0914; PR-957; LMP7
    Anti-inflammatory activity in human PBMC assessed as inhibition of LPS-induced IL-12/23 p40 production pretreated for 1 hr followed by LPS stimulation measured after 20 hrs
    Anti-inflammatory activity in human PBMC assessed as inhibition of LPS-induced IL-12/23 p40 production pretreated for 1 hr followed by LPS stimulation measured after 20 hrs
    [PMID: 28435528]
    PBMC IC50
    0.22 μM
    Compound: 3; ONX 0914; PR-957; LMP7
    Anti-inflammatory activity in human PBMC assessed as inhibition of LPS-induced GMCSF production pretreated for 1 hr followed by LPS stimulation measured after 20 hrs
    Anti-inflammatory activity in human PBMC assessed as inhibition of LPS-induced GMCSF production pretreated for 1 hr followed by LPS stimulation measured after 20 hrs
    [PMID: 28435528]
    PBMC IC50
    0.24 μM
    Compound: 3; ONX 0914; PR-957; LMP7
    Anti-inflammatory activity in human PBMC assessed as inhibition of LPS-induced IL-6 production pretreated for 1 hr followed by LPS stimulation measured after 20 hrs
    Anti-inflammatory activity in human PBMC assessed as inhibition of LPS-induced IL-6 production pretreated for 1 hr followed by LPS stimulation measured after 20 hrs
    [PMID: 28435528]
    PBMC IC50
    0.56 μM
    Compound: 3; ONX 0914; PR-957; LMP7
    Anti-inflammatory activity in human PBMC assessed as inhibition of LPS-induced TNF-alpha production pretreated for 1 hr followed by LPS stimulation measured after 20 hrs
    Anti-inflammatory activity in human PBMC assessed as inhibition of LPS-induced TNF-alpha production pretreated for 1 hr followed by LPS stimulation measured after 20 hrs
    [PMID: 28435528]
    PBMC IC50
    1.11 μM
    Compound: 3; ONX 0914; PR-957; LMP7
    Anti-inflammatory activity in human PBMC assessed as inhibition of LPS-induced IL-8 production pretreated for 1 hr followed by LPS stimulation measured after 20 hrs
    Anti-inflammatory activity in human PBMC assessed as inhibition of LPS-induced IL-8 production pretreated for 1 hr followed by LPS stimulation measured after 20 hrs
    [PMID: 28435528]
    PBMC IC50
    1.47 μM
    Compound: 3; ONX 0914; PR-957; LMP7
    Anti-inflammatory activity in human PBMC assessed as inhibition of LPS-induced Il-1b production pretreated for 1 hr followed by LPS stimulation measured after 20 hrs
    Anti-inflammatory activity in human PBMC assessed as inhibition of LPS-induced Il-1b production pretreated for 1 hr followed by LPS stimulation measured after 20 hrs
    [PMID: 28435528]
    PBMC IC50
    3.4 μM
    Compound: 3; ONX 0914; PR-957; LMP7
    Cytotoxicity against human PBMC assessed as decrease in cell viability by CellTiter-Glo assay
    Cytotoxicity against human PBMC assessed as decrease in cell viability by CellTiter-Glo assay
    [PMID: 28435528]
    PC-3 EC50
    0.33 μM
    Compound: ONX-0914
    Cytotoxicity against human PC3 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    Cytotoxicity against human PC3 cells assessed as reduction in cell viability after 48 hrs by Hoechst 33342 staining based HCS assay
    [PMID: 29339252]
    Raji IC50
    >10 μM
    Compound: 1, ONX-0914
    Inhibition of 20s proteasome subunit beta-1c in human Raji cells using BODIPY- epoxomicin by fluorescent densitometry
    Inhibition of 20s proteasome subunit beta-1c in human Raji cells using BODIPY- epoxomicin by fluorescent densitometry
    [PMID: 25006746]
    Raji IC50
    0.46 μM
    Compound: 1, ONX-0914
    Inhibition of proteasome subunit beta-1i in human Raji cells using BODIPY- epoxomicin by fluorescent densitometry
    Inhibition of proteasome subunit beta-1i in human Raji cells using BODIPY- epoxomicin by fluorescent densitometry
    [PMID: 25006746]
    Raji IC50
    0.59 μM
    Compound: 1, ONX-0914
    Inhibition of proteasome subunit beta-2i in human Raji cells using BODIPY- epoxomicin by fluorescent densitometry
    Inhibition of proteasome subunit beta-2i in human Raji cells using BODIPY- epoxomicin by fluorescent densitometry
    [PMID: 25006746]
    Raji IC50
    1.1 μM
    Compound: 1, ONX-0914
    Inhibition of 20s proteasome subunit beta-2c in human Raji cells using BODIPY- epoxomicin by fluorescent densitometry
    Inhibition of 20s proteasome subunit beta-2c in human Raji cells using BODIPY- epoxomicin by fluorescent densitometry
    [PMID: 25006746]
    Raji IC50
    5.7 nM
    Compound: 1, ONX-0914
    Inhibition of proteasome subunit beta-5i in human Raji cells using BODIPY-NC005 by fluorescent densitometry
    Inhibition of proteasome subunit beta-5i in human Raji cells using BODIPY-NC005 by fluorescent densitometry
    [PMID: 25006746]
    Raji IC50
    54 nM
    Compound: 1, ONX-0914
    Inhibition of 20s proteasome subunit beta-5c in human Raji cells using BODIPY-NC005 by fluorescent densitometry
    Inhibition of 20s proteasome subunit beta-5c in human Raji cells using BODIPY-NC005 by fluorescent densitometry
    [PMID: 25006746]
    RPMI-8226 IC50
    >5 μM
    Compound: 1, ONX-0914
    Inhibition of 20s proteasome subunit beta-1c in human RPMI8226 cells using BODIPY-NC001 by fluorescent densitometry
    Inhibition of 20s proteasome subunit beta-1c in human RPMI8226 cells using BODIPY-NC001 by fluorescent densitometry
    [PMID: 25006746]
    RPMI-8226 IC50
    0.018 μM
    Compound: 1, ONX-0914
    Inhibition of proteasome subunit beta-5i in human RPMI8226 cells using BODIPY-NC005 by fluorescent densitometry
    Inhibition of proteasome subunit beta-5i in human RPMI8226 cells using BODIPY-NC005 by fluorescent densitometry
    [PMID: 25006746]
    RPMI-8226 IC50
    0.18 μM
    Compound: 1, ONX-0914
    Inhibition of 20s proteasome subunit beta-5c in human RPMI8226 cells using BODIPY-NC005 by fluorescent densitometry
    Inhibition of 20s proteasome subunit beta-5c in human RPMI8226 cells using BODIPY-NC005 by fluorescent densitometry
    [PMID: 25006746]
    RPMI-8226 IC50
    0.34 μM
    Compound: 1, ONX-0914
    Inhibition of proteasome subunit beta-1i in human RPMI8226 cells using BODIPY-NC001 by fluorescent densitometry
    Inhibition of proteasome subunit beta-1i in human RPMI8226 cells using BODIPY-NC001 by fluorescent densitometry
    [PMID: 25006746]
    RPMI-8226 IC50
    0.59 μM
    Compound: 1, ONX-0914
    Inhibition of proteasome subunit beta-2i in human RPMI8226 cells using BODIPY-epoxomicin by fluorescent densitometry
    Inhibition of proteasome subunit beta-2i in human RPMI8226 cells using BODIPY-epoxomicin by fluorescent densitometry
    [PMID: 25006746]
    RPMI-8226 IC50
    0.68 μM
    Compound: 4; ONX-091
    Antiproliferative activity against human RPMI-8226 cells assessed as inhibition of cell proliferation after 72 hrs by MTS assay
    Antiproliferative activity against human RPMI-8226 cells assessed as inhibition of cell proliferation after 72 hrs by MTS assay
    [PMID: 34087498]
    RPMI-8226 IC50
    1.1 μM
    Compound: 1, ONX-0914
    Inhibition of 20s proteasome subunit beta-2c in human RPMI8226 cells using BODIPY-epoxomicin by fluorescent densitometry
    Inhibition of 20s proteasome subunit beta-2c in human RPMI8226 cells using BODIPY-epoxomicin by fluorescent densitometry
    [PMID: 25006746]
    体外実験

    ONX-0914 inhibits LMP7-specific antigen presentation. ONX-0914 blocks cytokine productionby mouse splenocytes and blocks T celldifferentiation[1].

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

    体内実験

    ONX-0914 (2-10 mg/kg; i.v,; on days 4, 6 and 8) meliorates disease in mouse arthritis[1].
    ? ONX-0914 (2, 6 and 10 mg per kg body weight on days 25, 27, 29, 31 and 33; i.v.) treatment also induced a rapid therapeutic response in the T and B cell–dependent CIA (collagen-induced arthritis) model[1].

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

    Animal Model: Collagen antibody-induced arthritis (CAIA, Arthritis was induced in BALB/c mice with antibodies specific for type II collagen (mAb) and endotoxin)[1]
    Dosage: 2, 6 or 10 mg per kg body weight
    Administration: I.v.; treated on days 4, 6 and 8
    Result: Blocked disease progression in a dose-dependent manner and completely ameliorated visible signs of disease at the highest dose.
    分子量

    580.67

    分子式

    C31H40N4O7

    CAS 番号
    Appearance

    Solid

    Color

    White to yellow

    SMILES

    O=C(N[C@@H](C)C(N[C@@H](CC1=CC=C(OC)C=C1)C(N[C@@H](CC2=CC=CC=C2)C([C@]3(C)OC3)=O)=O)=O)CN4CCOCC4

    輸送条件

    Room temperature in continental US; may vary elsewhere.

    保管条件
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    溶剤 & 溶解度
    体外: 

    DMSO : 100 mg/mL (172.21 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.7221 mL 8.6107 mL 17.2215 mL
    5 mM 0.3444 mL 1.7221 mL 3.4443 mL
    10 mM 0.1722 mL 0.8611 mL 1.7221 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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    体内:

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    • Protocol 1

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.17 mg/mL (3.74 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.17 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (21.7 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.17 mg/mL (3.74 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.17 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (21.7 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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    純度とドキュメンテーション

    純度: 99.72%

    参考文献

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.7221 mL 8.6107 mL 17.2215 mL 43.0537 mL
    5 mM 0.3444 mL 1.7221 mL 3.4443 mL 8.6107 mL
    10 mM 0.1722 mL 0.8611 mL 1.7221 mL 4.3054 mL
    15 mM 0.1148 mL 0.5740 mL 1.1481 mL 2.8702 mL
    20 mM 0.0861 mL 0.4305 mL 0.8611 mL 2.1527 mL
    25 mM 0.0689 mL 0.3444 mL 0.6889 mL 1.7221 mL
    30 mM 0.0574 mL 0.2870 mL 0.5740 mL 1.4351 mL
    40 mM 0.0431 mL 0.2153 mL 0.4305 mL 1.0763 mL
    50 mM 0.0344 mL 0.1722 mL 0.3444 mL 0.8611 mL
    60 mM 0.0287 mL 0.1435 mL 0.2870 mL 0.7176 mL
    80 mM 0.0215 mL 0.1076 mL 0.2153 mL 0.5382 mL
    100 mM 0.0172 mL 0.0861 mL 0.1722 mL 0.4305 mL
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    Inquiry Information

    製品名:
    ONX-0914
    製品番号:
    HY-13207
    数量:
    MCE 日本正規代理店: