Alectinib

Alectinib (CH5424802; RO5424802; RG7853) is a potent, selective, and orally available ALK inhibitor with an IC₅₀ of 1.9 nM and a K_d value of 2.4 nM (in an ATP-competitive manner), and also inhibits ALK F1174L and ALK R1275Q with IC₅₀s of 1 nM and 3.5 nM, respectively^[1]. Alectinib demonstrates effective central nervous system (CNS) penetration^[2]. IC50 & Target:IC50: 1.9 nM(ALK), 1 nM (ALK^F1174L), 3.5 nM (ALK^R1275Q)^[1]
Kd: 2.4 nM (ALK)^[1] In Vitro:Alectinib (0-1000 nM; 2 hours; NCI-H2228 cells) treatment could prevent autophosphorylation of ALK in NCI-H2228 cells expressing EML4-ALK, and it also resulted in substantial suppression of phosphorylation of STAT3 and AKT^[1].
Alectinib (0-1000 nM; 5 days; HCC827, A549, or NCIH522 cells) treatment reduces cell activity in a dose-dependent manner^[1]. In Vivo:Alectinib (0.2-20 mg/kg; oral administration; once daily; for 11 days; SCID or nude mice bearing NCI-H2228 cells) treatment can result in dose-dependent tumor growth inhibition (EC₅₀ of 0.46 mg/kg) and tumor regression. At any dose level, no differences in body weight or gross signs of toxicity are observed^[1].