Alectinib 是一种有效的、选择性的、口服具有活力的、ATP 竞争性的ALK抑制剂，其IC50=1.9 nM，Kd=2.4 nM，并且还抑制ALK F1174L和ALK R1275Q，其IC50分别为 1 nM 和 3.5 nM。它还有中枢神经系统渗透能力。

CH5424802 is an orally available inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) with antineoplastic activity.

在小鼠中,CH5424802（20 mg/kg）处理能够抑制肿瘤生长.CH5424802 (2-20 mg/kg)以剂量依赖的方式抑制STAT3磷酸化.

在表达EML4-ALK的NCI-H2228NSCLC细胞中,CH5424802防止ALK自磷酸化。 在NCI-H2228球状体细胞中, CH5424802诱导凋亡标记 - 半胱天冬酶-3/7样活化。 在淋巴瘤细胞系KARPAS-299和SR与NPM-ALK中, CH5424802阻断融合蛋白的生长。CH5424802对天然ALK（Ki=0.83 nM）和L1196M（Ki=1.56 nM）都具有显着的抑制效力。 CH5424802抑制KAPRAS-299（IC50=3 nM）,KDR（IC50=1.4 μM）。

Kinase inhibitory assays in Vitro: The inhibitory ability against each kinase except for MEK1 and Raf-1 is evaluated by examining their ability to phosphorylate various substrate peptides in the presence of CH5424802 using time-resolved fluorescence resonance energy transfer (TR-FRET) assay or fluorescence polarization (FP) assay. The inhibitory activity against MEK1 is evaluated by quantitative analysis of the phosphorylation of a substrate peptide by a recombinant ERK2 protein in the presence of CH5424802. The inhibitory activity against Raf-1 is evaluated by examining the ability of the kinases to phosphorylate MEK1 in the presence of CH5424802.

Cells including NSCLC, A549 and HCC827 are seeded in 96-well plates overnight and incubated with various concentrations of CH5424802 for the indicated time. For spheroid cell growth inhibition assay, cells are seeded on spheroid plates, incubated overnight, and then treated with compound for the indicated times. The viable cells are measured by the Luminescent Cell Viability Assay. Caspase-3/7 assay is evaluated using the Caspase-Glo 3/7 Assay Kit.(Only for Reference)

1256580-46-7

C30H34N4O2

482.628

AF802;AF-802;CH5424802;RG-7853;艾乐替尼

H2O:2.1 mM
DMSO:12.4 mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years