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)。
| 生物活性 | Oprozomib (PR-047) is an orally bioavailable and selective peptide epoxyketoneproteasomeinhibitor withIC50s of 36 and 82 nM forproteasome(β5) and immunoproteasome (LMP7), respectively. Oprozomib (ONX 0912) inducesapoptosisin MM cells[1]. |
体外研究
(In Vitro) | Oprozomib inhibits 20S chymotrypsin-like (CT-L) with an IC50of 55 ± 19 nM. Oprozomib inhibits human leukemia Molt-4 cells CT-L with an IC50of 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].
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. |
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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].
| 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. |
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| 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 |
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| 溶解性数据 | In Vitro: DMSO : ≥ 50 mg/mL(93.88 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 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。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin 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 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 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本网站选购。
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