1. Cell Cycle/DNA Damage
    Protein Tyrosine Kinase/RTK
    Autophagy
  2. Deubiquitinase
    Bcr-Abl
    Autophagy

WP1130 (Synonyms: Degrasyn)

Cat. No.: HY-13264 Purity: 99.72%
Data Sheet SDS Handling Instructions

WP1130 inhibits the autoactivation of Bcr-Abl by inducing its rapid down-regulation with IC50 of 1.8 μM. WP1130 also is a deubiquitinase inhibitor.

For research use only. We do not sell to patients.
WP1130 Chemical Structure

WP1130 Chemical Structure

CAS No. : 856243-80-6

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $76 In-stock
5 mg $69 In-stock
10 mg $125 In-stock
50 mg $495 In-stock
100 mg $850 In-stock
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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

WP1130 inhibits the autoactivation of Bcr-Abl by inducing its rapid down-regulation with IC50 of 1.8 μM. WP1130 also is a deubiquitinase inhibitor.

IC50 & Target

IC50: 1.8 μM (Bcr-Abl)[1]
Deubiquitinase[2]

In Vitro

WP1130, a small molecule that specifically and rapidly down-regulates both wild-type and mutant Bcr/Abl protein without affecting bcr/abl gene expression in chronic myelogenous leukemia (CML) cells. WP1130 is more effective in inducing apoptosis of myeloid and lymphoid tumor cells (IC50 0.5 to 2.5 μM) than normal CD34+ hematopoietic precursors, dermal fibroblasts, or endothelial cells (IC50 ~5 to 10 μM). WP1130 reduces Bcr/Abl protein levels through a unique mechanism that is not affected by mutations that interfere with imatinib mesylate binding. WP1130 inhibits phosphorylation of both the wild-type and the T315I mutant Bcr/Abl proteins, as demonstrated by the rapid disappearance (within 1 hour) of phosphotyrosyl-Bcr/Abl in both BV173 and BV173R cells. WP1130-induced down-regulation of Bcr/Abl is accompanied by apoptosis of CML cells[1]. Treatment with WP1130 yields an anti-proliferative effect across all cell lines tested in a dose-dependent manner. Notably, treatment with WP1130 results in marked anti-proliferative activity and morphological changes in NCH644 and NCH421K glioma stem-like cells. Treatment with WP1130 results in a dose-dependent and probably compensatory increase of Mcl-1 mRNA levels after 6 h and only a minor decrease after 24 h. Similar findings are observed for Usp9X levels. These data suggest that WP1130 down-regulates Mcl-1 and Usp9X through a post-transcriptional mechanism[2].

In Vivo

WP1130 suppresses the growth of K562 heterotransplanted tumors as well as both wild-type Bcr/Abl and T315I mutant Bcr/Abl-expressing BaF/3 cells transplanted into nude mice. To assess the possible therapeutic activity of WP1130 against CML, nude mice received a subcutaneous transplant with K562 cells and are treated with 30 mg/kg WP1130 every other day for 9 days after palpable tumor formation (10 days). This dose and schedule are well tolerated and effective in other tumor models. Antitumor activity is compared with that after daily Imatinib mesylate treatment (50 mg/kg). Nineteen days after tumor inoculation, tumors in the control group reached maximum allowable dimension, and the effect of therapy is assessed. WP1130 treatment suppresses K562 tumor growth to an extent comparable to that observed in imatinib mesylate-treated animals, suggesting that WP1130 is active in reducing the growth of established K562 tumors[1].

References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 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
Cell Assay
[1]

WP1130 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1].

CML cells are seeded in 96-well plates (2×104 cells/well) and WP1130, Imatinib mesylate, or Dasatinib (0.08-10 μM) are added in a final volume of 100 μL medium. Plates are incubated at 37°C for 72 hours, after which 20 μL of MTT reagent (stock 5 mg/mL) is added, and the plates are incubated at 37°C for another 2 hours. Cells are lysed with 100 μL lysis buffer (20% 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[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

WP1130 is prepared in DMSO and PEG300 (Mice)[1].

Mice[1]
To assess activity against T315I Bcr/Abl mutant cells, BaF/3 cells transfected with wild-type Bcr/Abl or the T315I mutant are transplanted into female Swiss nude mice (5-6 weeks old). BaF/3wt cells are suspended (5×107 cells/mL) in RPMI medium, and 0.1 mL of this suspension is injected intravenously into 10 mice. The same procedure is used to inoculate 10 mice with BaF/3/T315I cells. One day after tumor cell inoculation, mice are randomly assigned to 1 of 3 groups: one group received WP1130 (40 mg/kg, intraperitoneally) in 50 μL DMSO/PEG300 (vehicle) every other day (7 injections); another received imatinib mesylate (100 mg/kg, intraperitoneally) in vehicle daily (14 injections); and the third received vehicle alone daily (14 injections). Spleens from each mouse are harvested, photographed, and weighed 15 days after tumor cell inoculation. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

384.27

Formula

C₁₉H₁₈BrN₃O

CAS No.

856243-80-6

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 33 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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