Degrasyn (WP1130)

Catalog No.S2243

Degrasyn (WP1130) Chemical Structure

Molecular Weight(MW): 384.27

Degrasyn (WP1130) is a selective deubiquitinase (DUB: USP5, UCH-L1, USP9x, USP14, and UCH37) inhibitor and also suppresses Bcr/Abl, also a JAK2 transducer (without affecting 20S proteasome) and activator of transcription (STAT).

Size Price Stock Quantity  
In DMSO USD 260 In stock
USD 170 In stock
USD 320 In stock
USD 970 In stock

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3 Customer Reviews

  • Protein expression by western blot analysis of cell lysates from MCF-7, TAMR-4 and 164R-7 cells treated for 3 days with vehicle (0.1% DMSO), 1 uM or 1.5 uM WP1130.

    Oncogene 2014 10.1038/onc.2014.351. Degrasyn (WP1130) purchased from Selleck.

    The inhibitors of DUBs and UBE1 inhibited HSV-2 replication. HEC-1-A cells were either infected or not infected in the presence of WP1130 (2 ug/ml) or PYR-41 (20 ug/ml). Levels of ubiquitin conjugates, IκB-α, and gD were determined 24 h p.i.

    J Virol 2013 87(15), 8675-86. Degrasyn (WP1130) purchased from Selleck.

  • USP9X activity regulates Mcl-1 expression. (b) A549 cells were plated in 10 cm tissue culture dishes and upon reaching 70% confluency were treated with 10 μg/ml CHX for 6 h or exposed to a combination of 7.5 μM WP1130 for 2, 4 and 6 h and 10 μg/ml CHX for 6 h. Mcl-1 and USP9X signals were then determined by western blotting. Proteins were quantified using UN-SCAN-IT. Those intensities of the signals of USP-9X and Mcl-1 are relative to Actin.

    BMC Cancer 2012 12, 541. Degrasyn (WP1130) purchased from Selleck.

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2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description Degrasyn (WP1130) is a selective deubiquitinase (DUB: USP5, UCH-L1, USP9x, USP14, and UCH37) inhibitor and also suppresses Bcr/Abl, also a JAK2 transducer (without affecting 20S proteasome) and activator of transcription (STAT).
Features WP1130 has an advantage over imatinib mesylate in that its activity is not inhibited by a variety of Abl kinase mutations, including T315I.
Targets
DUB [1]
(Cell-free assay)
Bcr-Abl [1]
(Cell-free assay)
1.8 μM
In vitro

In addition to inducing rapid down-regulation of Bcr/Abl without affecting Bcr or c-Abl, WP1130 also regulates the stability of Jak2 and c-Myc without affecting other kinases (HER1, HER2, c-Kit, FAK, ERK1, ERK2, Akt, Btk, Src and Src-related kinases) or transcription factors (wild-type p53, STAT1, STAT3, STAT5, c-Jun, NF-κB, and Max). Unlike adaphostin and Trisenox, WP1130 induces down-regulation of Bcr/Abl within 60 minutes. WP1130 is more effective in inducing apoptosis of myeloid and lymphoid tumor cells with IC50 of ~0.5-2.5 μM compared with normal CD34+ hematopoietic precursors, dermal fibroblasts, or endothelial cells with IC50 of ~5-10 μM. WP1130 (5 μM) specifically and rapidly down-regulates both wild-type and T315I mutant Bcr/Abl protein without affecting bcr/abl gene expression or engaging the proteasomal degradation pathway in chronic myelogenous leukemia (CML) cells, accompanied by induction of apoptosis. WP1130 is more effective in reducing leukemic cell colony formation compared with normal progenitor cells, and effective against primary leukemic cells harboring the T315I mutation. [1] WP1130 induces rapid proteasomal-dependent degradation of c-Myc protein in MM-1 multiple myeloma and other tumor cell lines, correlated with tumor growth inhibition. [2] Unlike AG490, WP1130 acts as a partly selective deubiquitinase (DUB) inhibitor to induce a rapid and marked accumulation of polyubiquitinated (K48/K63-linked) proteins into juxtanuclear aggresomes without affecting proteasome activity. WP1130 (5 μM) directly inhibits DUB activity of USP9x, USP5, USP14, UCH-L1, and UCH37, but not UCH-L3, resulting in downregulation of antiapoptotic and upregulation of proapoptotic proteins, such as MCL-1 and p53. [3]

In vivo Administration of WP1130 inhibits the growth of K562 tumors as well as both wildtype Bcr/Abl and T315I mutant Bcr/Abl-expressing BaF/3 cells transplanted into nude mice. [1] Consistent with the down-regulation of c-Myc, WP1130 displays potent inhibitory activity against A375 melanoma tumors established in nude mice. [2]

Protocol

Cell Research:[1]
+ Expand
  • Cell lines: BV173, BV173R, K562, and BaF/3
  • Concentrations: Dissolved in DMSO, final concentrations ~10 μM
  • Incubation Time: 72 hours
  • Method: Cells are treated with increasing concentrations of WP1130 (0.08-10 μM) in 96-well plates. Plates are incubated at 37 °C for 72 hours, after which 20 μL of MTT reagent is added, and the plates are incubated at 37 °C for another 2 hours. Cells are lysed with 100 μL lysis buffer (20% sodium dodecyl sulfate [SDS] in 50% N, N-dimethylformamide adjusted to pH 4.7 with 80% acetic acid and 1 M hydrochloric acid; final concentration of acetic acid is 2.5% and hydrochloric acid is 2.5%) and incubated for 6 hours. The optical density of each sample at 570 nm is determined with a SPECTRA MAX M2 plate reader.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Swiss Nu/Nu mice transplanted with K562 tumor cells, BaF/3wt cells, or BaF/3/T315I cells
  • Formulation: Formulated in solution of 1:1 dimethylsulfoxide to polyethylene glycol 300
  • Dosages: ~40 mg/kg every other day
  • Administration: Injected intraperitoneally
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 77 mg/mL (200.37 mM)
Ethanol 18 mg/mL (46.84 mM)
Water <1 mg/mL

* 1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 384.27
Formula

C19H18BrN3O

CAS No. 856243-80-6
Storage powder
in solvent
Synonyms N/A

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID