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

ONX-0914 (PR-957) 是選擇性的低分子量多肽-7 (LMP7) 的抑制劑，LMP7 是免疫蛋白酶體的類糜蛋白酶亞單位。ONX-0914 阻斷細(xì)胞因子的產(chǎn)生并減輕實(shí)驗(yàn)性關(guān)節(jié)炎的進(jìn)展。ONX-0914 是分枝桿菌蛋白酶體的非競(jìng)爭(zhēng)性不可逆抑制劑 (Ki=5.2 μM)。ONX-0914 通過 HSF-1 介導(dǎo)的 p-TEFb 活化激活潛伏的 HIV-1。

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ONX-0914 Chemical Structure

ONX-0914 Chemical Structure

CAS No. : 960374-59-8

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規(guī)格 價(jià)格 是否有貨 數(shù)量
10 mM * 1 mL in DMSO ￥1916
In-stock
1 mg ￥681
In-stock
5 mg ￥1500
In-stock
10 mg ￥2400
In-stock
25 mg ￥4800
In-stock
50 mg 現(xiàn)貨 詢價(jià)
100 mg 現(xiàn)貨 詢價(jià)
200 mg   詢價(jià)  
500 mg   詢價(jià)  

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Customer Review

Other Forms of ONX-0914:

    ONX-0914 purchased from MCE. 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.

    ONX-0914 purchased from MCE. 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 MCE. 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.

    查看 HIV 亞型特異性產(chǎn)品:

    • 生物活性

    • 純度 & 產(chǎn)品資料

    • 參考文獻(xiàn)

    生物活性

    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

     

    細(xì)胞效力
    (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]
    體外研究
    (In Vitro)

    ONX-0914 抑制 LMP7 特異性抗原呈遞。ONX-0914 阻斷小鼠脾細(xì)胞產(chǎn)生細(xì)胞因子并阻斷 T 細(xì)胞分化[1]。

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    體內(nèi)研究
    (In Vivo)

    ONX-0914 (2-10 mg/kg；靜脈注射；在第 4、6 和 8 天) 改善小鼠關(guān)節(jié)炎的疾病[1]。
    ONX-0914 (第 2、6 和在第 25、27、29、31 和 33 天，每公斤體重 10 毫克；iv) 處理還在 T 和 B 細(xì)胞依賴性 CIA (膠原誘導(dǎo)的關(guān)節(jié)炎) 模型中誘導(dǎo)了快速處理反應(yīng)[1]。

    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

    Formula

    C31H40N4O7
    CAS 號(hào)
    性狀

    固體

    顏色

    White to yellow

    運(yùn)輸條件

    Room temperature in continental US; may vary elsewhere.
    儲(chǔ)存方式
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 6 months
    -20°C 1 month
    溶解性數(shù)據(jù)
    細(xì)胞實(shí)驗(yàn)： 

    DMSO 中的溶解度 : ≥ 35 mg/mL (60.28 mM; 吸濕的 DMSO 對(duì)產(chǎn)品的溶解度有顯著影響，請(qǐng)使用新開封的 DMSO)

    * "≥" means soluble, but saturation unknown.

    配制儲(chǔ)備液
    濃度 溶劑體積 質(zhì)量 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
    查看完整儲(chǔ)備液配制表

    * 請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；一旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
    儲(chǔ)備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)月內(nèi)使用，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)月內(nèi)使用。

    • 摩爾計(jì)算器

    • 稀釋計(jì)算器

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    質(zhì)量
    =
    濃度
    ×
    體積
    ×
    分子量 *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    濃度 (start)

    C1

    ×
    體積 (start)

    V1

    =
    濃度 (final)

    C2

    ×
    體積 (final)

    V2

    動(dòng)物實(shí)驗(yàn)：

    請(qǐng)根據(jù)您的 實(shí)驗(yàn)動(dòng)物和給藥方式 選擇適當(dāng)?shù)娜芙夥桨浮?

    以下溶解方案都請(qǐng)先按照 In Vitro 方式配制澄清的儲(chǔ)備液，再依次添加助溶劑：
    ——為保證實(shí)驗(yàn)結(jié)果的可靠性，澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的工作液，建議您現(xiàn)用現(xiàn)配，當(dāng)天使用；
    以下溶劑前顯示的百分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的方式助溶

    • 方案 一

      請(qǐng)依序添加每種溶劑： 10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.17 mg/mL (3.74 mM); 澄清溶液

      此方案可獲得 ≥ 2.17 mg/mL（飽和度未知）的澄清溶液。

      以 1 mL 工作液為例，取 100 μL 21.7 mg/mL 的澄清 DMSO 儲(chǔ)備液加到 400 μL PEG300 中，混合均勻；再向上述體系中加入 50 μL Tween-80，混合均勻；然后再繼續(xù)加入 450 μL 生理鹽水 定容至 1 mL。

      生理鹽水的配制：將 0.9 g 氯化鈉，溶解于 ddH?O 并定容至 100 mL，可以得到澄清透明的生理鹽水溶液。
    • 方案 二

      請(qǐng)依序添加每種溶劑： 10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.17 mg/mL (3.74 mM); 澄清溶液

      此方案可獲得 ≥ 2.17 mg/mL（飽和度未知）的澄清溶液。

      以 1 mL 工作液為例，取 100 μL 21.7 mg/mL 的澄清 DMSO 儲(chǔ)備液加到 900 μL 20% 的 SBE-β-CD 生理鹽水水溶液 中，混合均勻。

      2 g SBE-β-CD（磺丁基醚 β-環(huán)糊精）粉末定容于 10 mL 的生理鹽水中，完全溶解至澄清透明。
    動(dòng)物溶解方案計(jì)算器
    請(qǐng)輸入動(dòng)物實(shí)驗(yàn)的基本信息：

    給藥劑量

    mg/kg

    動(dòng)物的平均體重

    g

    每只動(dòng)物的給藥體積

    μL

    動(dòng)物數(shù)量

    只
    由于實(shí)驗(yàn)過程有損耗，建議您多配一只動(dòng)物的量
    請(qǐng)輸入您的動(dòng)物體內(nèi)配方組成：
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    如果您的動(dòng)物是免疫缺陷鼠或者體弱鼠，建議 DMSO 中的在最后工作液體系中的占比盡量不超過 2%。
    方案所需 助溶劑 包括：DMSO， ，均可在 MCE 網(wǎng)站選購。 ，Tween 80，均可在 MCE 網(wǎng)站選購。
    計(jì)算結(jié)果
    工作液所需濃度 : mg/mL
    儲(chǔ)備液配制方法 : mg 藥物溶于 μL  DMSO（母液濃度為 mg/mL）。
    您所需的儲(chǔ)備液濃度超過該產(chǎn)品的實(shí)測(cè)溶解度，以下方案僅供參考，如有需要，請(qǐng)與 MCE 中國(guó)技術(shù)支持聯(lián)系。
    動(dòng)物實(shí)驗(yàn)體內(nèi)工作液的配制方法 : 取 μL DMSO 儲(chǔ)備液，加入 μL 。 μL ，混合均勻至澄清，再加 μL Tween 80，混合均勻至澄清，再加 μL 生理鹽水。
    連續(xù)給藥周期超過半月以上，請(qǐng)謹(jǐn)慎選擇該方案。
    請(qǐng)確保第一步儲(chǔ)備液溶解至澄清狀態(tài)，從左到右依次添加助溶劑。您可采用超聲加熱 （超聲清洗儀，建議頻次 20-40 kHz），渦旋吹打等方式輔助溶解。
    純度 & 產(chǎn)品資料

    純度: 99.72%

    參考文獻(xiàn)

    完整儲(chǔ)備液配制表

    * 請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；一旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
    儲(chǔ)備液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)月內(nèi)使用，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)月內(nèi)使用。

    可選溶劑 濃度 溶劑體積 質(zhì)量 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
    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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