Rearranged during transfection (RET) is a receptor tyrosine kinase that acts as an oncogenic driver in multiple cancers. BLU-667 is a potent, selective, small-molecule RET inhibitor that demonstrates ≥10-fold increased potency over other multi-kinase inhibitors. It inhibited the kinase activity of wild-type RET with an IC50 of 0.4nM. BLU-667 also exhibited potent inhibitory activity against common oncogenic RET alterations, including RET V804L, RET V804M, RET M918T, and CCDC6-RET fusion, with IC50 values of 0.3, 0.4, 0.4, and 0.4nM, respectively. In Ba/F3 cells engineered to express a KIF5B-RET fusion, treatment with BLU-667 inhibited RET autophosphorylation with a cellular IC50 value of 5nM. BLU-667 also inhibited phosphorylation of RET, SHC, and ERK1/2 at concentrations of ≤10nM in RET-driven cell lines. In RET-driven murine models, BLU667 at doses as low as 10mg/kg (twice per day) exhibited concentration-dependent activity against KIF5B-RET Ba/F3 and KIF5B-RET V804L Ba/F3 allograft tumors. BLU-667 at doses of 3 to 60mg/kg also showed potent activity in a RET C634W MTC xenograft, and KIF5B-RET NSCLC and CCDC6-RET CRC patient-derived xenograft models[1].
RET-altered Non Small Cell Lun... 展开 >>g Cancer
Medullary Thyroid Cancer
RET-altered Papillary Thyroid Cancer
RET-altered Colon Cancer
RET-altered Solid Tumors 收起 <<
RET-altered Non Small Cell Lun... 展开 >>g Cancer
Medullary Thyroid Cancer
RET-altered Papillary Thyroid Cancer
RET-altered Colon Cancer
RET-altered Solid Tumors 收起 <<
搜索
