Selumetinib

Selumetinib (AZD6244) is selective, non-ATP-competitive oral MEK1/2 inhibitor, with an IC₅₀ of 14 nM for MEK1. Selumetinib (AZD6244) inhibits ERK1/2 phosphorylation. Selumetinib can penetrate the blood brain barrier (BBB)^[1][2][3][4]. IC50 & Target:IC50: 12 nM (MEK)^[4], 14 nM (MEK1)^[3] In Vitro: Selumetinib (AZD6244) causes a time- and dose-dependent reduction in DNA synthesis and cell viability in primary, induces growth arrest and apoptosis associated with the inactivation of ERK in primary 2-1318 cells^[1].
Selumetinib (AZD6244) (1μM) shows anti-proliferative effects through G0/G1 arrest on H-441, H-1437 cells^[2].
Selumetinib (AZD6244) results in the growth inhibition of several cell lines containing B-Raf and Ras mutations but has no effect on a normal fibroblast cell line^[3]. In Vivo: Selumetinib (AZD6244, 50 and 100 mg/kg, p.o.) decreases the growth rate of 4-1318 xenografts in a dose-dependent manner; AZD6244 when given at the dose of 50 mg/kg also significantly suppresses the growth of the 5-1318, 2-1318, 26-1004, and 29-1104 xenografts^[1]. Selumetinib (ARRY-142886, 10, 25, 50, or 100 mg/kg, p.o.) is capable of inhibiting both ERK1/2 phosphorylation and growth of HT-29 xenograft tumors in nude mice. Tumor regressions are also seen in a BxPC3 xenograft model^[3].