NSC 687852 (b-AP15)
(Synonyms: b-AP15) 目录号 : GC15503
An inhibitor of the deubiquitinases USP14 and UCHL5
Cas No.:1009817-63-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
Bacterial lipopolysaccharide (LPS)-primed macrophages prepared from adult male C57BL/6 mice(Harlan)LPS-primed THP-1 cells(to induce pro-IL-1β expression before nigericin treatment) |
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Preparation method |
The solubility of this compound in DMSO is >21mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1μM |
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Applications |
Pretreatment with NSC 687852 inhibited ATP-induced IL-1β release from LPS-primed peritoneal macrophages and nigericin-induced release from LPS-primed THP-1 cells and reduced the levels of cell death induced by nigericin treatment in THP-1 cells. In macrophages, NSC 687852 also caused an increase in polyubiquitinated proteasomal substrates. In LPS-primed THP-1 cells, NSC 687852 significantly reduced the numbers of ASC specks formed after nigericin treatment. Similarly, ATP-induced speck formation in murine peritoneal macrophages was also inhibited by NSC 687852. |
| Animal experiment [2]: | |
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Animal models |
combined immunodeficiency (SCID) mice with FaDu squamous carcinoma xenografts;mice with HCT-116 colon carcinoma xenografts overexpressing BCL2 |
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Dosage form |
daily subcutaneous injection ;5 mg per kg of body weight |
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Application |
When administered NSC 687852 daily to severe combined immunodeficiency (SCID) mice with FaDu squamous carcinoma xenografts, there was a significant antitumor activity. When analyzed tumor death by measuring xenograft-derived CK18 in circulation, there was a significant increase in the plasma concentrations of total CK18 as well as increased concentrations of caspase-cleaved CK18 (CK18-Asp396) , showing that NSC 687852 had activity against tumor cells in vivo. When also examined disease-free survival in mice with HCT-116 colon carcinoma xenografts overexpressing BCL2, NSC 687852 treatment significantly delayed tumor onset compared to vehicle-treated controls, with two out of six of the mice treated with NSC 687852 being completely disease free at the end of the study. |
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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]. Lopez-Castejon G,Luheshi NM,Compan V., et al. Deubiquitinases regulate the activity of caspase-1 and interleukin-1β secretion via assembly of the inflammasome. J Biol Chem.2013 Jan 25;288(4):2721-33. doi: 10.1074/jbc.M112.422238. Epub 2012 Dec 3. [2]. D'Arcy P,Brnjic S,Olofsson MH., et al. Inhibition of proteasome deubiquitinating activity as a new cancer therapy. Nat Med.2011 Nov 6;17(12):1636-40. doi: 10.1038/nm.2536. |
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IC50: N/A
NSC 687852 is a 19S regulatory particle inhibitor.
The 19S particles bind polyubiquitin-linked polypeptides and present them to the 20S degradative units. USP14 and UCHL5 are cysteine enzymes that become activated after being associated with the proteasome.
In vitro: NSC 687852 blocked deubiquitylating activity of USP14 and UCHL5 selectively without inhibiting proteasome activity. NSC 687852 decreased viability in multiple myeloma (MM) cell lines and patient MM cells, inhibited MM cell proliferation even in the presence of bone marrow stroma cells, and overcomed bortezomib resistance. Anti-MM activity of NSC 687852 was associated with growth arrest through downregulating CDC2, CDC25C, and cyclin B1, as well as induction of caspase-dependent apoptosis and activation of unfolded protein response [1].
In vivo: In vivo studies using distinct human MM xenograft models showed that NSC 687852 was well tolerated, inhibited tumor growth, and prolonged mouse survival. Combination of NSC 687852 with suberoylanilide hydroxamic acid, lenalidomide, or dexamethasone was found to induce synergistic anti-MM activity [1].
Clinical trial: N/A
Reference:
[1] Ze Tian,Padraig D'Arcy,Xin Wang,Arghya Ray,Yu-Tzu Tai,Yiguo Hu,Ruben D Carrasco,Paul Richardson,Stig Linder,Dharminder Chauhan,Kenneth C Anderson. A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Blood. 2014 Jan 30; 123(5): 706–716.
| Cas No. | 1009817-63-3 | SDF | |
| 别名 | b-AP15 | ||
| 化学名 | (3E,5E)-3,5-bis[(4-nitrophenyl)methylidene]-1-prop-2-enoylpiperidin-4-one | ||
| Canonical SMILES | C=CC(=O)N1CC(=CC2=CC=C(C=C2)[N+](=O)[O-])C(=O)C(=CC3=CC=C(C=C3)[N+](=O)[O-])C1 | ||
| 分子式 | C22H17N3O6 | 分子量 | 419.39 |
| 溶解度 | ≥ 20.95mg/mL in DMSO | 储存条件 | Store at 4°C,unstable in solution, ready to use. |
| 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 | 2.3844 mL | 11.9221 mL | 23.8442 mL |
| 5 mM | 0.4769 mL | 2.3844 mL | 4.7688 mL |
| 10 mM | 0.2384 mL | 1.1922 mL | 2.3844 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。