Degrasyn (WP1130)

Catalog No.S2243 Batch:S224302

Print

Technical Data

Formula

C19H18BrN3O
Molecular Weight 384.27 CAS No. 856243-80-6
Solubility (25°C)* In vitro DMSO 77 mg/mL (200.37 mM)
Ethanol 50 mg/mL (130.11 mM)
Water Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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). Degrasyn (WP1130) induces apoptosis and blocks autophagy.
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]
Features WP1130 has an advantage over imatinib mesylate in that its activity is not inhibited by a variety of Abl kinase mutations, including T315I.

Protocol (from reference)

Cell Assay:[1]
  • 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.
Animal Study:[1]
  • Animal Models

    Swiss Nu/Nu mice transplanted with K562 tumor cells, BaF/3wt cells, or BaF/3/T315I cells

  • Dosages

    ~40 mg/kg every other day

  • Administration

    Injected intraperitoneally

Customer Product Validation

Data from [Data independently produced by Oncogene, 2014, 10.1038/onc.2014.351]

Data from [Data independently produced by J Virol, 2013, 87(15), 8675-86]

Data from [BMC Cancer, 2012, 12, 541]

Data from [Data independently produced by , , Cancer Res, 2016, 76(8):2384-93]

Selleck's Degrasyn (WP1130) has been cited by 43 publications

Mechanisms of MCL-1 Protein Stability Induced by MCL-1 Antagonists in B-Cell Malignancies [ Clin Cancer Res, 2023, 29(2):446-457] PubMed: 36346691
Ubiquitin-specific peptidase 5 facilitates cancer stem cell-like properties in lung cancer by deubiquitinating β-catenin [ Cancer Cell Int, 2023, 23(1):207] PubMed: 37726816
Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer-In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models [ Biomedicines, 2023, 10.3390/biomedicines11030759] PubMed: 36979739
Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer-In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models [ Biomedicines, 2023, 11(3)759] PubMed: 36979739
USP5-Beclin 1 axis overrides p53-dependent senescence and drives Kras-induced tumorigenicity [ Nat Commun, 2022, 13(1):7799] PubMed: 36528652
USP9x promotes CD8 + T-cell dysfunction in association with autophagy inhibition in septic liver injury [ Acta Biochim Biophys Sin (Shanghai), 2022, 54(12):1-10] PubMed: 36514222
Elevated USP9X drives early-to-late-stage oral tumorigenesis via stabilisation of anti-apoptotic MCL-1 protein and impacts outcome in oral cancers [ Br J Cancer, 2021, 10.1038/s41416-021-01421-x] PubMed: 34079080
Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2 [ Cell Chem Biol, 2021, S2451-9456(21)00213-0] PubMed: 33979649
USP9X deubiquitinates connexin43 to prevent high glucose-induced epithelial-to-mesenchymal transition in NRK-52E cells [ Biochem Pharmacol, 2021, 188:114562] PubMed: 33857489
Deubiquitinating enzyme inhibitor alleviates cyclin A1-mediated proteasome inhibitor tolerance in mixed-lineage leukemia [ Cancer Sci, 2021, 112(6):2287-2298] PubMed: 33738896

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.