Oprozomib (ONX-0912)
(Synonyms: ONX-0912,ONX0912,ONX 0912,PR 047,Oprozomib) 目录号 : GC15447
An orally available proteasome inhibitor
Cas No.:935888-69-0
Sample solution is provided at 25 µL, 10mM.
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ONX-0912 (as known as oprozomib), discovered during a medicinal chemistry effort using tripeptide epoxyketones, is an orally bio-available and potent proteasome inhibitor that inhibits growth and induces apoptosis in bortezomib resistant multiple myeloma (MM) cells. Although ONX-0912, an analog of carfilzomib, is structurally distinct from bortezomib, it possesses the same ability as bortezomib to predominantly inhibit chymotrypsin-like activity of the proteasome. ONX-0912 exhibits significant anti-MM activities to reduce tumor progression and prolong survival in many animal tumor model studies, which are associated with activation of caspase-3, caspase-8, caspase-9, and poly(ADP) ribose polymerase and inhibition of anglogensis and MM cells migration.
Reference
[1]Dharminder Chauhan, Ajita V. Singh, Monette Aujay, Christopher J. Kirk, Madhavi Bandi, Bryan Ciccarelli, Noopur Raje, Paul Richardson, and Kenneth C. Anderson. A novel oraaly active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood 2010; 116(23): 4906-4915
| Cell experiment: | |
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Cell lines |
The human HNSCC cell lines UMSCC-22A, UMSCC-22B, 1483, UMSCC-1, and Cal33. |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
48 h; IC50 values ranging from 58.9 to185.7 nmol/L in 8 different HNSCC cell lines. |
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Applications |
In trypan blue exclusion assays, ONX 0912 exhibited IC50 values ranging from 58.9 to185.7 nmol/L in 8 different HNSCC cell lines. In the 4 HNSCC cell lines (UMSCC-1, UMSCC-22B, 1483, and UMSCC-1) examined, treatment ONX 0912 resulted in processing of caspase-3 to active subunits and cleavage of the caspase substrate PARP. |
| Animal experiment: | |
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Animal models |
Athymic nude mice |
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Dosage form |
30 mg/kg; Oral taken. |
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Applications |
Using nude mice harboring HNSCC xenograft tumors, oral administration of 30 mg/kg ONX 0912 effectively inhibited CT-L activity in normal and HNSCC tumor tissues. Treatments (10 mg/kg and 30 mg/kg) were administered via oral gavage once a day on 2 consecutive days and repeated weekly for 2 weeks. Treatment with 10 mg/kg ONX 0912 did not have a significant effect on tumor growth, relative to treatment with vehicle alone. In contrast, highly significant inhibition of HNSCC tumor growth was seen with 30 mg/kg ONX 0912 (P = 0.003). These results show that consecutive-day treatment with orally administered ONX 0912, using a dose that has previously been shown to be well tolerated, leads to inhibition of HNSCC tumor growth. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Zang Y, Thomas S M, Chan E T, et al. Carfilzomib and ONX 0912 inhibit cell survival and tumor growth of head and neck cancer and their activities are enhanced by suppression of Mcl-1 or autophagy[J]. Clinical Cancer Research, 2012, 18(20): 5639-5649. | |
| Cas No. | 935888-69-0 | SDF | |
| 别名 | ONX-0912,ONX0912,ONX 0912,PR 047,Oprozomib | ||
| 化学名 | N-[(2S)-3-methoxy-1-[[(2S)-3-methoxy-1-[[(2S)-1-[(2R)-2-methyloxiran-2-yl]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-2-methyl-1,3-thiazole-5-carboxamide | ||
| Canonical SMILES | CC1=NC=C(S1)C(=O)NC(COC)C(=O)NC(COC)C(=O)NC(CC2=CC=CC=C2)C(=O)C3(CO3)C | ||
| 分子式 | C25H32N4O7S | 分子量 | 532.61 |
| 溶解度 | ≥ 26.6mg/mL in DMSO | 储存条件 | Desiccate at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet