CEP-18770
(Synonyms: CEP-18770) 目录号 : GC12272
An inhibitor of chymotrypsin-like proteasome activity
Cas No.:847499-27-8
Sample solution is provided at 25 µL, 10mM.
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CEP-18770 is a novel, potent and reversible P2 threonine boronic acid inhibitor of proteasome that inhibits proteasome’s chymotrypsin-like activity, with the value of inhibition constant IC50 of 3.8 nM, by down-modulating the activity of nuclear factor-KB (NF-KB) as well as the expression of a few NF-KB downstream effectors. Preliminary results of multiple studies have shown that CEP-18770 exerts potent antitumor activities against human multiple myeloma (MM) cell lines by inducing apoptotic cell death, exhibits a strong antiangiogenic activity suppressing RANKL-induced osteoclastogenesis, and displays a favorable cytotoxicity profile towards normal cells including epithelial cells, bone marrow progenitors, and bone marrow-derived stromal cells.
Reference
[1].Piva R, Ruggeri B, Williams M, Costa G, Tamagno I, Ferrero D, Giai V, Coscia M, Peola S, Massaia M, Pezzoni G, Allievi C, Pescalli N, Cassin M, di Giovine S, Nicoli P, de Feudis P, Strepponi I, Roato I, Ferracini R, Bussolati B, Camussi G, Jones-Bolin S, Hunter K, Zhao H, Neri A, Palumbo A, Berkers C, Ovaa H, Bernareggi A, Inghirami G. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood. 2008;111(5):2765-2775
| Cell experiment: [1] | |
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Cell lines |
RPMI-8226 cells |
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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 |
40 nM, 4 to 8 hours |
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Applications |
As an inhibitor of proteasome, CEP-18770 induced an accumulation of ubiquitinated proteins over 4 to 8 hours with a profile similar to that observed after bortezomib (another proteasome inhibitor) treatment. |
| Animal experiment : [1] | |
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Animal models |
SCID mice bearing human MM RPMI 8226 subcutaneous xenograft |
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Dosage form |
Intravenous (from 1 to 6 mg/kg, 2q7d×8 injections) or oral administration (in a solution of 3% DMSO, 10% Solutol, and 87% sterile NaCl 0.9%, twice-a-week injections for 4 weeks at doses of 7.8, 10, 13 mg/kg in a volume of 20 mL/kg body weight of mouse). |
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Applications |
Intravenous administration of CEP-18770 exhibited sustained and dose-related tumor weight inhibition with RTWI of 100% at all tested doses. CEP-18770 also exhibited dose-related increases in the incidence of tumor-free mice by the completion of the studies (120 days after tumor transplantation) within the 3- and 4-mg/kg intravenous treatment groups, 89% and 80%, respectively. Oral administration of CEP-18770 resulted in a significant reduction of tumor weight and notable dose-related incidence of complete tumor regression (75% incidence of CR and 25% tumor-free mice at 10 mg/kg orally). |
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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] Piva R, Ruggeri B, Williams M, et al. CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood, 2008, 111(5): 2765-2775. | |
| Cas No. | 847499-27-8 | SDF | |
| 别名 | CEP-18770 | ||
| 化学名 | [(1R)-1-[[(2S,3R)-3-hydroxy-2-[(6-phenylpyridine-2-carbonyl)amino]butanoyl]amino]-3-methylbutyl]boronic acid | ||
| Canonical SMILES | B(C(CC(C)C)NC(=O)C(C(C)O)NC(=O)C1=CC=CC(=N1)C2=CC=CC=C2)(O)O | ||
| 分子式 | C21H28BN3O5 | 分子量 | 413.3 |
| 溶解度 | ≥ 16.75 mg/mL in DMSO, ≥ 32.27 mg/mL in EtOH with ultrasonic | 储存条件 | Store 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.4195 mL | 12.0977 mL | 24.1955 mL |
| 5 mM | 0.4839 mL | 2.4195 mL | 4.8391 mL |
| 10 mM | 0.242 mL | 1.2098 mL | 2.4195 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet