379231-04-6

Storage:at -20℃ 2 years

Biologieal

WP1130 is a novel selective small molecular deubiquitinase (DUB) inhibitor and a Bcr/Abl destruction pathway activator with an IC50 of 1.8 μM for K562 cells. WP1130 acts as a partly selective deubiquitinases (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 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 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. Collectively, WP1130 reduces wild-type and T315I mutant Bcr/Abl protein levels in CML cells through a unique mechanism and may be useful in treating CML^.[1][2]

Reference

[1] Bartholomeusz GA et al. Blood. 2007 Apr 15; 109(8):3470-8.