AZD-3463是一种具有口服活性的ALK/IGF1R抑制剂，对 ALK 作用的Ki值为 0.75 nM。它可诱导神经母细胞瘤细胞凋亡和自噬。

AZD3463, an orally bioavailable ALK inhibitor (Ki: 0.75 nM), can inhibit IGF1R with equivalent potency.

在体内,AZD-3463对突变型L1196M和野生型ALK的作用同等有效.在体内作用于移植瘤时,AZD-3463剂量依赖性抑制pALK,使肿瘤体积停滞（H3122）或衰退（DEL,H2228）.

在各种体外耐Crizotinib模型中,AZD3463对六分之五的细胞具有抗增殖的效力,4倍于亲本H3122细胞。AZD3463对含ALK融合的肿瘤细胞系均有效果,包括DEL(ALCL NPM-ALK),H2228(NSCLC EML4-ALK)和H3122(NSCLC EML4-ALK),抑制ALK并降低其自身磷酸化。

HDAC enzymatic assays: Tubastatin A is dissolved and diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, and 20 μM tris(2-carboxyethyl)phosphine) to 6-fold of the final concentration. HDAC enzymes are diluted to 1.5-fold of the final concentration in assay buffer and pre-incubated with Tubastatin A for 10 minutes before the addition of the substrate. The amount of FTS (HDAC1, HDAC2, HDAC3, and HDAC6) or MAZ-1675 (HDAC4, HDAC5, HDAC7, HDAC8, and HDAC9) used for each enzyme is equal to the Michaelis constant (Km), as determined by a titration curve. FTS or MAZ-1675 is diluted in assay buffer to 6-fold the final concentration with 0.3 μM sequencing grade trypsin. The substrate/trypsin mix is added to the enzyme/compound mix and the plate is shaken for 60 seconds and then placed into a SpectraMax M5 microtiter plate reader. The enzymatic reaction is monitored for release of 7-amino-4-methoxy-coumarin over 30 minutes, after deacetylation of the lysine side chain in the peptide substrate, and the linear rate of the reaction is calculated.

1356962-20-3

C24H25ClN6O

448.95

ALK/IGF1R inhibitor

Ethanol:<1 mgml
DMSO:23 mg/mL (51.2 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years