Degrasyn_product_DataBase

Bioactivity

Degrasyn (WP1130) is a cell-permeable deubiquitinase (DUB) inhibitor, directly inhibiting DUB activity of USP9x, USP5, USP14, and UCH37. Degrasyn has been shown to downregulate the antiapoptotic proteins Bcr-Abl and JAK2.

Invitro

Degrasyn, 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. Degrasyn 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). Degrasyn reduces Bcr/Abl protein levels through a unique mechanism that is not affected by mutations that interfere with imatinib mesylate binding. Degrasyn 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. Degrasyn-induced down-regulation of Bcr/Abl is accompanied by apoptosis of CML cells[1]. Treatment with Degrasyn yields an anti-proliferative effect across all cell lines tested in a dose-dependent manner. Notably, treatment with Degrasyn results in marked anti-proliferative activity and morphological changes in NCH644 and NCH421K glioma stem-like cells. Treatment with Degrasyn 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 Degrasyn down-regulates Mcl-1 and Usp9X through a post-transcriptional mechanism[2].

Name

Degrasyn

CAS

856243-80-6

Formula

C19H18BrN3O

Molar Mass

384.27

Transport

Room temperature in continental US; may vary elsewhere.

Storage

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

PeptideDB

Degrasyn

CAS: 856243-80-6 F: C19H18BrN3O W: 384.27