WP1130 (Synonyms: WP 1130; WP-1130) |
Catalog No.GC10970
One-Click Copy Product Info
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WP1130 (WP1130) is a cell-permeable deubiquitinase (DUB) inhibitor, directly inhibiting DUB activity of USP9x, USP5, USP14, and UCH37. WP1130 has been shown to downregulate the antiapoptotic proteins Bcr-Abl and JAK2.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 856243-80-6
Sample solution is provided at 25 µL, 10mM.
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WP1130, also known as degrasyn, is a second-generation tyrphostin derivative initially identified as a Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathway inhibitor that reduces STAT activation stimulated by cytokines (such as IL-6 and IL-3) through the rapid down-regulation of upstream JAK kinases. WP1130 has also been identified as a selective deubiquitinating enzyme (DUB) inhibitor that directly inhibits DUB activity of USP9x, USP5, USP14 and UCH37 leading to rapid accumulation of polyubiquitinated proteins into juxtanuclear aggresomes and tumor cell apoptosis. WP1130-induced apoptosis and anti-proliferation in tumor cells have been implicated in the treatment of chronic myelogenous leukemia (CML), melanoma, glioblastoma and myeloproliferative disorders.
References:
[1]Kapuria V1, Peterson LF, Fang D, Bornmann WG, Talpaz M, Donato NJ. Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis. Cancer Res. 2010 Nov 15;70(22):9265-76. doi: 10.1158/0008-5472.CAN-10-1530. Epub 2010 Nov 2.
[2]Bartholomeusz GA1, Talpaz M, Kapuria V, Kong LY, Wang S, Estrov Z, Priebe W, Wu J, Donato NJ. Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells. Blood. 2007 Apr 15;109(8):3470-8. Epub 2007 Jan 3.
| Cell experiment [1]: | |
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Cell lines |
The human typical MCL cell lines (Mino, DB, Z-138, and JMP-1) |
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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; EC50=~1 μM |
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Applications |
Degrasyn (WP1130) had superior inhibitory activity in the JAK/STAT pathway and the antiproliferative effect. These studies showed that cell growth suppression was seen in all three compounds(WP1130, WP1129 and WP1066 for all four cell lines, and the half maximal effective concentration (EC50) of degrasyn was lower than that of the other two compounds in all four MCL cell lines, suggesting that degrasyn is a more effective anti-tumor agent in MCL cells. |
| Animal experiment [1]: | |
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Animal models |
Young SCID mice |
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Dosage form |
20 mg/kg; i.p. |
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Applications |
Useing a xenotransplant SCID mouse model of MCL. Degrasyn alone showed modest prolongation of survival compared with vehicle alone (P<0.105). In addition, normal control mice (n = 5) given treatment with degrasyn alone or in combination with bortezomib remained alive and showed no signs of body weight loss. |
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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] Pham L V, Tamayo A T, Li C, et al. Degrasyn potentiates the antitumor effects of bortezomib in mantle cell lymphoma cells in vitro and in vivo: therapeutic implications[J]. Molecular cancer therapeutics, 2010, 9(7): 2026-2036. | |
| Cas No. | 856243-80-6 | SDF | |
| Synonyms | WP 1130; WP-1130 | ||
| Chemical Name | (E)-3-(6-bromopyridin-2-yl)-2-cyano-N-[(1S)-1-phenylbutyl]prop-2-enamide | ||
| Canonical SMILES | CCCC(C1=CC=CC=C1)NC(=O)C(=CC2=NC(=CC=C2)Br)C#N | ||
| Formula | C19H18BrN3O | M.Wt | 384.27 |
| Solubility | ≥ 38.4mg/mL in DMSO | Storage | Store at -20°C |
| 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 | 2.6023 mL | 13.0117 mL | 26.0234 mL |
| 5 mM | 520.5 μL | 2.6023 mL | 5.2047 mL |
| 10 mM | 260.2 μL | 1.3012 mL | 2.6023 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 saline, 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: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 40 reference(s) in Google Scholar.)