NSC 687852 (b-AP15) (Synonyms: b-AP15) |
| カタログ番号GC15503 |
An inhibitor of the deubiquitinases USP14 and UCHL5
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1009817-63-3
Sample solution is provided at 25 µL, 10mM.
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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.
| 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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| Cas No. | 1009817-63-3 | SDF | |
| 同義語 | b-AP15 | ||
| Chemical Name | (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 | ||
| Formula | C22H17N3O6 | M.Wt | 419.39 |
| 溶解度 | ≥ 20.95mg/mL in DMSO | Storage | Store at 4°C,unstable in solution, ready to use. |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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