ALK-IN-26 is an ALK inhibitor with IC50 value of 7.0 μM for ALK tyrosine kinase. ALK-IN-26 has good pharmacokinetic properties and blood-brain barrier (BBB) permeability. ALK-IN-26 can induce apoptosis, autophagy and necrosis. ALK-IN-26 can be used in glioblastoma studies.
ALK-IN-26 (0.5-2 μM, 24 h) can inhibit the activity of ALK in GL216 cells[1].ALK-IN-26 (0.5-2 μM, 24 h) can reduce the expression of mTOR protein in GL216 cells [1].[1].ALK-IN-26 (0.5-2 μM, 24 h) significantly decreases p-ERK1/2 protein level and enhances p-JNK protein level in GL261 and U87MG cells, while has little effect on p-AKT and p-STAT3 protein levels[1].ALK-IN-26 (0.5μM-2.0 μM, 24h) can induce autophagy in GL261 cells[1].ALK-IN-26 (0.5 μM-0.5 μM, 24-72 h) increases the protein levels of cleaved-PARP (c-PARP) and cleaved-caspase-3 (c-caspase 3) in GL261 cells[1].ALK-IN-26 (0.5 μM-2μM, 24-72 h) induces apoptosis in GL261 cells[1].
ALK-IN-26 (5 mg/kg, i.v., single dose) has pharmacokinetic properties in male C57BL6/J mice[1].ALK-IN-26 is (20 mg/kg, i.p., single dose) able to penetrate the blood-brain barrier in male C57BL6/J mice[1].Pharmacokinetic parameters of C57BL6/J in male rats (n = 3) [1]
References:
[1]. Feng L, et al. Synthesis and Bioevaluation of 3-(Arylmetlene) indole Derivatives: Discovery of a Novel ALK Modulator with Antiglioblastoma Activities[J]. Journal of Medicinal Chemistry, 2023.