Brief Description

WP1130(Degrasyn) is a novel selective small molecular deubiquitinase (USP5, UCH-L1, USP9x, USP14, and UCH37) inhibitor and a Bcr/Abl destruction pathway activator with an IC50 of 1.8 μM for K562 cells.
Target: Deubiquitinase
in vitro: WP1130 acts as a partly selective DUB inhibitor, directly inhibiting DUB activity of USP9x, USP5, USP14, and UCH37, which are known to regulate survival protein stability and 26S proteasome function. WP1130-mediated inhibition of tumor-activated DUBs results in downregulation of antiapoptotic and upregulation of proapoptotic proteins, such as MCL-1 and p53. WP1130 did not affect Hsp90/Hsp70 ratios within the cells and did not require the participation of the proteasomal pathway for loss of Bcr/Abl protein. WP1130 was more effective in reducing leukemic versus normal hematopoietic colony formation and strongly inhibited colony formation of cells derived from patients with T315I mutant Bcr/Abl-expressing CML in blast crisis.
in vivo: WP1130 suppressed 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. Consistent with the down-regulation of c-Myc, WP1130 displays potent inhibitory activity against A375 melanoma tumors established in nude mice.

Solubility

DMSO ≥75mg/mL; Water <1.2mg/mL; Ethanol ≥75mg/mL

Melting point

Boiling point

Density

Formula Weight:

Flash point

Storage conditions

Store at -20°C 2 years

Appearance:

White to off-white solid