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| 25mg |
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| 50mg |
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Purity: ≥98%
Degrasyn (formerly also known as WP1130) is a novel, potent, and selective small molecule inhibitor of deubiquitinases (DUBs such as USP5, USP14, USP9x, UCH-L1, and UCH37). It also suppresses Bcr/Abl, also a JAK2 transducer without affecting 20S proteasome and an activator of transcription (STAT). It exhibits excellent in vivo antitumor efficacy in Swiss Nu/Nu mice transplanted with K562 tumor cells.
| ln Vitro |
Degrasyn is a tiny molecule that, in chronic myelogenous leukemia (CML) cells, selectively and quickly down-regulates both wild-type and mutant Bcr/Abl protein without changing the expression of the bcr/abl gene. Because of its distinct mechanism of reducing Bcr/Abl protein levels, degrasyn is more effective in inducing apoptosis in myeloid and lymphoid tumors. This mechanism is unaffected by mutations that interfere with imatinib mesylate binding. Degrasyn prevents the phosphorylation of Bcr/Abl proteins, both wild-type and T315I mutant. This is indicated by the quick disappearance of phosphotyrosyl-Bcr/Abl in both BV173 and BV173R cells, which occurs within an hour. The down-regulation of Bcr/Abl brought on by degrasyn causes CML cells to undergo apoptosis[1]. Applying Degrasyn treatment has a dose-dependent anti-proliferative effect on all tested cell lines. Notably, NCH644 and NCH421K glioma stem-like cells treated with degrasyn exhibit strong anti-proliferative activity as well as morphological alterations. After 6 hours, treatment with Degrasyn causes a dose-dependent and likely compensatory increase in Mcl-1 mRNA levels, and after 24 hours, there is only a slight decrease. Comparable results are noted for Usp9X concentrations. These findings imply that Degrasyn uses a post-transcriptional mechanism to downregulate Mcl-1 and Usp9X[2].
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| ln Vivo |
The growth of K562 heterotransplanted tumors and Bcr/Abl wild-type and T315I mutant Bcr/Abl-expressing BaF/3 cells transplanted into nude mice are both suppressed by degrasyn. Nude mice that received a subcutaneous transplant of K562 cells are administered with 30 mg/kg Degrasyn every other day for nine days following the development of a palpably palpable tumor (10 days) in order to evaluate the potential therapeutic effectiveness of Degrasyn against CML. In other tumor models, this dosage and timing are efficient and well-tolerated. The antitumor activity is contrasted with the results of a daily 50 mg/kg dose of imatinib mesylate treatment. Tumors in the control group attained their maximum permissible dimension nineteen days after the tumor was inoculated, and the effectiveness of the treatment was evaluated. Treatment with Degrasyn inhibits the growth of K562 tumors to a degree similar to that seen in mice treated with imatinib mesylate, indicating that Degrasyn is effective in slowing the growth of K562 tumors that have already grown[1].
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| References |
| Molecular Formula |
C19H18BRN3O
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| Molecular Weight |
384.27
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| Exact Mass |
383.063
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| CAS # |
856243-80-6
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| Related CAS # |
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| PubChem CID |
11222830
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
582.1±50.0 °C at 760 mmHg
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| Flash Point |
305.9±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.617
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| LogP |
4.01
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
24
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| Complexity |
490
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCC[C@@H](C1=CC=CC=C1)NC(=O)/C(=C/C2=NC(=CC=C2)Br)/C#N
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| InChi Key |
LIDOPKHSVQTSJY-VMEIHUARSA-N
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| InChi Code |
InChI=1S/C19H18BrN3O/c1-2-7-17(14-8-4-3-5-9-14)23-19(24)15(13-21)12-16-10-6-11-18(20)22-16/h3-6,8-12,17H,2,7H2,1H3,(H,23,24)/b15-12+/t17-/m0/s1
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| Chemical Name |
(E)-3-(6-bromopyridin-2-yl)-2-cyano-N-[(1S)-1-phenylbutyl]prop-2-enamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6023 mL | 13.0117 mL | 26.0234 mL | |
| 5 mM | 0.5205 mL | 2.6023 mL | 5.2047 mL | |
| 10 mM | 0.2602 mL | 1.3012 mL | 2.6023 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
WP1130 reduces the growth of CML tumors and Bcr/Abl-expressing cells in nude mice.Blood.2007 Apr 15;109(8):3470-8. |
Down-regulation of Bcr/Abl protein by WP1130 is not associated with changes in Hsp70 and is not suppressed by protease inhibition.Blood.2007 Apr 15;109(8):3470-8. |
WP1130 reduces the viability of cells expressing wild-type and mutant Bcr/Abl.Blood.2007 Apr 15;109(8):3470-8. |
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