Stemcell, 72992, AZD6244

AZD6244 is a potent, highly selective inhibitor of the mitogen-activated protein kinases MEK1 (IC₅₀ = 14 nM) and MEK2 (Kd = 530 nM; Yeh et al.; Davis et al.). It is a tight-binding noncompetitive inhibitor that does not bind in the ATP binding pocket of MEK (Huynh et al.). It also shows micromolar binding to epidermal growth factor receptor (EGFR; Davis et al.).

CANCER RESEARCH

· Inhibits growth of several tumor cell lines but not normal fibroblast lines, and inhibits tumor growth in a colorectal xenograft tumor model (Yeh et al.).

· Inhibits proliferation and induces differentiation and apoptosis in multiple tumor cell lines and tumor xenograft models, especially those containing BRAF or RAS mutations (Davies et al.).

· Inhibits proliferation of breast cancer and non-small cell lung cancer cell lines, especially those containing RAF and RAS mutations, respectively (Garon et al.).