货号：A7209

储存条件：粉末-20°C可保存3年；液体-80°C可保存12月。

产品描述

HSP90 (heat shock protein 90) is a cellular ubiquitous molecular chaperone responsible for promoting the conformational mutation and stabilization of several client oncoproteins, including Met, B-Raf, p53, Akt, and Kit, function of which is required by tumor cells to maintain appropriate client protein expression necessary for proliferation and survival. 17-AAG is a geldanamycin-derived HSP90 inhibitor with 100-fold higher binding affinity for Hsp90 derived from tumour cells (IC50=6nM, measured by competitive binding assays using a biotinylated GM probe) than normal cells, which may due to the high ATPase activity of tumour Hsp90 by co-chaperones. Exposure to 5μM 17-AAG reduced Bcr-Abl protein levels in HL-60/Bcr-Abl and K562 cells, and also down-regulated the levels of c-Raf in Bcr-Abl-positive cells and the control HL-60/neo cells. Induced cell apoptosis of HL-60/neo, HL-60/Bcr-Abl and K562 cells can be observed after exposure to 5μM 17-AAG for 24-72h. Intraperitoneal injection with 17-AAG at different doses ranging in 5-40mg/kg every other day for three weeks prolonged the survival of mice injected with TGB lymphoma cells. Administration of 40mg/kg 17-AAG effectively impaired the self-renewal of the lymphoma CSCs in vivo.

作用机制

1. 17-AAG is a geldanamycin-derived HSP90 inhibitor which can bind to the N-terminal ATP/ADP-binding domain of Hsp90.

2. As tumour cells gradually accumulate mutant and over expressed signalling proteins, this makes HSP90 become engaged in active chaperoning and stabilization of oncoproteins. This will make HSP90 adopt a high affinity form induced by bound co-chaperone proteins and make HSP90 possess higher activity in tumour cells. This can explain why 17-AAG showed higher binding affinity for Hsp90 derived from tumour cells.

产品信息