Oprozomib(Synonyms: ONX 0912; PR-047)

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Oprozomib (Synonyms: ONX 0912; PR-047) 纯度: 99.71%

Oprozomib (PR-047) 是一种有效的，具有口服活性的选择性肽环氧酮类蛋白酶体 (proteasome) 抑制剂，对蛋白酶体 (β5) 和免疫蛋白酶体 (LMP7) 的 IC50 分别为 36 和 82 nM。 Oprozomib (ONX 0912) 诱导多发性骨髓瘤细胞凋亡 (apoptosis)。

Oprozomib(Synonyms: ONX 0912; PR-047)

Oprozomib Chemical Structure

CAS No. : 935888-69-0

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ￥1308 In-stock
5 mg ￥1116 In-stock
10 mg ￥1488 In-stock
50 mg ￥7149 In-stock
100 mg ￥10008 In-stock
200 mg   询价  
500 mg   询价  

* Please select Quantity before adding items.

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生物活性

Oprozomib (PR-047) is an orally bioavailable and selective peptide epoxyketone proteasome inhibitor with IC50s of 36 and 82 nM for proteasome (β5) and immunoproteasome (LMP7), respectively. Oprozomib (ONX 0912) induces apoptosis in MM cells[1].

体外研究
(In Vitro)

Oprozomib inhibits 20S chymotrypsin-like (CT-L) with an IC50 of 55 ± 19 nM. Oprozomib inhibits human leukemia Molt-4 cells CT-L with an IC50 of 66 nM[1].
Oprozomib (ONX 0912; 1-1000 nM; 48 hours) significantly decreases the viability of human multiple myeloma (MM) cell lines[2].
The anti-MM activity of Oprozomib is associated with activation of caspase-8, caspase-9, caspase-3, and PARP[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[2]

Cell Line: Human MM cell lines (MM.1S, INA-6, RPMI-8226, MM.1R, Dox-40, KMS12, and OPM2)
Concentration: 1, 10, 100, 1000 nM
Incubation Time: 48 hours
Result: Exhibited anti-MM activity.

Western Blot Analysis[2]

Cell Line: MM.1S cells
Concentration: 7 nM and 10 nM
Incubation Time: 48 hours
Result: Treatment with 3nM triggered a marked increase in proteolytic cleavage of PARP, a signature event during apoptosis. Induced cleavage of caspase-3, an upstream activator of PARP. Induced activation of both casapse-8 (extrinsic) and caspase-9 (intrinsic) apoptotic pathways.

体内研究
(In Vivo)

Oprozomib (PR-047) selectively inhibits chymotrypsin-like (CT-L) activity of both the constitutive proteasome (β5) and immunoproteasome (LMP7) and demonstrates an absolute bioavailability of up to 39% in rodents and dogs[1].
Oprozomib promotes antitumor activity in multiple animal models by oral administration at doses below the maximum tolerated dose (MTD)[1].
Oprozomib (30 mg/kg by oral gavage once daily for 5 consecutive days followed by 2 days of rest) treatment decreases tumor burden in C57Bl/6 and NOD.SCID.IL2Rγ-/- mice[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57Bl/6 and NOD.SCID.IL2Rγ-/- mice bearing established human RPMI-8226-luc myeloma cells[3]
Dosage: 30 mg/kg
Administration: Oral gavage once daily for 5 consecutive days followed by 2 days of rest
Result: Decreased human MM tumor burden and protects mice from bone destruction.

Clinical Trial

分子量

532.61

Formula

C25H32N4O7S
CAS 号

935888-69-0
中文名称

奥泼佐米
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : ≥ 50 mg/mL (93.88 mM)

* “≥” means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.8775 mL 9.3877 mL 18.7755 mL
5 mM 0.3755 mL 1.8775 mL 3.7551 mL
10 mM 0.1878 mL 0.9388 mL 1.8775 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.08 mg/mL (3.91 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (3.91 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.08 mg/mL (3.91 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (3.91 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
  • 3.

    请依序添加每种溶剂： 10% DMSO    90% corn oil

    Solubility: ≥ 2.08 mg/mL (3.91 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (3.91 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Han-Jie Zhou, et al. Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047). J Med Chem. 2009 May 14;52(9):3028-38.

    [2]. Dharminder Chauhan,et al. A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood. 2010 Dec 2;116(23):4906-15.

    [3]. M A Hurchla, et al.The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-anabolic activity in addition to anti-myeloma effects. Leukemia. 2013 Feb;27(2):430-40.

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