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GMB-475
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
GMB-475图片
CAS NO:2490599-18-1
包装与价格:
包装价格(元)
1 mg电议
5 mg电议
10 mg电议
25 mg电议
50 mg电议
100 mg电议
200 mg电议
1 mL*10 mM(in DMSO)电议

产品介绍
GMB-475 是一种基于PROTAC的Bcr-Abl1酪氨酸激酶降解剂,克服了Bcr-Abl1依赖的耐药性。 GMB-475 靶向 Bcr-Abl1 蛋白并募集 E3 连接酶 Von Hippel Lindau (VHL)。导致泛素化和随后的致癌融合蛋白降解

产品描述

GMB-475 is a BCR-ABL1 tyrosine kinase degrader based on PROTAC, overcoming BCR-ABL1-dependent drug resistance. GMB-475 targets BCR-ABL1 protein and recruits the E3 ligase Von Hippel Lindau (VHL).resulting in ubiquitination and subsequent degradation of the oncogenic fusion protein

体外活性

GMB-475 inhibited the proliferation of certain clinically relevant BCR-ABL1 kinase domain point mutants and further sensitized Ba/F3 BCR-ABL1 cells to inhibition by imatinib, while demonstrating no toxicity toward Ba/F3 parental cells.?Reverse phase protein array analysis suggested additional differences in levels of phosphorylated SHP2, GAB2, and SHC associated with BCR-ABL1 degradation.?Importantly, GMB-475 reduced viability and increased apoptosis in primary CML CD34+ cells, with no effect on healthy CD34+ cells at identical concentrations.?GMB-475 degraded BCR-ABL1 and reduced cell viability in primary CML stem cells.?Together, these findings suggest that combined BCR-ABL1 kinase inhibition and protein degradation may represent a strategy to address BCR-ABL1-dependent drug resistance, and warrant further investigation into the eradication of persistent leukemic stem cells, which rely on neither the presence nor the activity of the BCR-ABL1 protein for survival.

Cas No.

2490599-18-1

分子式

C43H4F3NOS

分子量

861.93

储存和溶解度

DMSO:95 mg/mL (110.22 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years