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WP1130

Cat. No. M1754
WP1130 Structure
Size Price Availability Quantity
10mg USD 130 In stock
50mg USD 500 In stock
100mg USD 820 In stock
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Quality Control
Biological Activity

WP1130 is a cell-permeable tyrphostin compound that acts as a partially selective deubiquitinase (DUB) inhibitor and suppresses JAK-Stat signaling pathway. Reported to cause accumulation of polyubiquitinated p53, JAK2 and Bcr-Abl, and reduce c-Myc and MCL-1 protein levels in several tumor cells and downregulate Stat3 and NF-κB activities (IC50 <1 µM in MCL cells) leading to tumor cell apoptosis (IC50 ~1.2 µM in Z138 cells). Suggested to modify active site cysteine of DUB and inhibit USP5, UCH-L1, USP9x, USP14, and UCH37 activities (≥80% inhibition at 5 µM) without affecting 20S proteasome. Reported to exert stronger antiproliferative and antitumor properties than STAT3 Inhibitor III, WP1066 in xenograft mouse models of CML and melanoma.

Protocol
Cell Experiment
Cell lines CML cells
Preparation method MTT (viability) assay CML cells were seeded in 96-well plates (2*104 cells/well) and WP1130, imatinib mesylate, or dasatinib (0.08-10 µ M) were added in a final volume of 100 µL medium. Plates were incubated at 37°C for 72 hours, after which 20 µL of 3-4,5-dimethylthiazolyl-2-2, 5-diphenyltetrazolium bromide (MTT) reagent (Sigma; stock 5 mg/mL) was added, and the plates were incubated at 37°C for another 2 hours. Cells were lysed with 100 L 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 was 2.5% and hydrochloric acid was 2.5%) and incubated for 6 hours. The optical density of each sample at 570 nm was determined with a SPECTRA MAX M2 plate reader (Molecular Devices, Sunnyvale, CA).
Concentrations 0.08-10 µ M
Incubation time 72 h
Animal Experiment
Animal models CML tumors and Bcr/Abl-expressing cells in nude mice
Formulation a 0.1-mL suspension of 1:1 dimethylsulfoxide to polyethylene glycol 300
Dosages 30 mg/kg every other day for 5 injections
Administration injected intraperitoneally
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 384.3
Formula C19H18BrN3O
CAS Number 856243-80-6
Purity >99%
Solubility DMSO
Storage at -20°C
References

Antiviral activity of a small molecule deubiquitinase inhibitor occurs via induction of the unfolded protein response.
Perry JW et al. PLoS Pathog. 2012 Jul;8(7):e1002783. PMID: 22792064.

A novel small molecule deubiquitinase inhibitor blocks Jak2 signaling through Jak2 ubiquitination.
Kapuria V et al. Cell Signal. 2011 Dec;23(12):2076-85. PMID: 21855629.

Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis.
Kapuria V et al. Cancer Res. 2010 Nov 15;70(22):9265-76. PMID: 21045142.

Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells.
Bartholomeusz GA et al. Blood. 2007 Apr 15;109(8):3470-8. PMID: 17202319.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: WP1130 supplier, JAK, inhibitors

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