Human epidermal growth factor receptor (EGFR; HER1,erbB1), human epidermal growth factor r eceptor 2 (HER2; erbB2), HER3 (erbB3) and HER4 (erbB4) are members of the ErbB family of transmembrane receptor tyrosine kinases. Among them, HER2 is a validated and high-value target. Overexpression of HER2 occurs in gastric, colorectal, NSCLC, breast and ovarian cancers. Mubritinib is a highly selective Her2 inhibitor with IC50 value of 6nM (measured by tyrosine-kinase activity), with almost no inhibition of other related target including EGFR, FGFR, PDGFR, Jak1, Src and Blk (all IC50 values>25000nM). Treatment with mubritinib at concentration>0.1μM for 2h caused significant decrease of autophosphorylation of Her2, as well as phosphorylation level of the key signal transduction mediator AKT and MAPK, in BT474 cells overexpressing HER2. The sensitivity of cell to Mubritinib depended on HER2 levels, as BT474 cells over-expressing HER2 strongly with highly sensitivity to Mubritinib (IC50=0.005µM), PC-3 cells expressing HER2 very weakly with less sensitive to Mubritinib (IC50=4.62µM), and HT1376 and ACHN cells over-expressed EGFR with much higher IC50 values (>25μM). Oral administration of 20mg/kg Mubritinib twice daily for 2 weeks significantly inhibited tumor growth in UMUC-3 bladder cancer model, as well as LN-REC4 prostate cancer model at dose of 10 or 20mg/kg[1].
United States, Arizona
... 展开 >>
Arizona Cancer Center
Scottsdale, Arizona, United States, 85258
United States, Texas
The Institute for Drug Development
San Antonio, Texas, United States, 78229
Brooke Army Medical Center/Drug Development Unit
San Antonio, Texas, United States, 78234
South Texas VA, Audie Murphy Division
San Antonio, Texas, United States, 78284 收起 <<
United States, Arizona
... 展开 >>
Arizona Cancer Center
Scottsdale, Arizona, United States, 85258
United States, Texas
The Institute for Drug Development
San Antonio, Texas, United States, 78229
Brooke Army Medical Center/Drug Development Unit
San Antonio, Texas, United States, 78234
South Texas VA, Audie Murphy Division
San Antonio, Texas, United States, 78284 收起 <<
搜索
