Name | AZD-3463 |
Description | AZD-3463 (ALK/IGF1R inhibitor) , an orally bioavailable ALK inhibitor (Ki: 0.75 nM), can inhibit IGF1R with equivalent potency. |
Kinase Assay | 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. |
In vitro | 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). |
In vivo | 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。 |
Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
Solubility Information | Ethanol : < 1 mg/mL (insoluble or slightly soluble) DMSO : 23 mg/mL (51.2 mM) H2O : < 1 mg/mL (insoluble or slightly soluble)
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Keywords | Anaplastic lymphoma kinase (ALK) | Anaplastic lymphoma kinase | Apoptosis | neuroblastoma | kinase | ALK | AZD3463 | receptor | PI3K/AKT/mTOR. pathway | crizotinib | CD246 | AZD-3463 | IGF-1R | resistance | ALK tyrosine kinase receptor | Inhibitor | inhibit | AZD 3463 | Cluster of differentiation 246 | tyrosine | Autophagy |
Inhibitors Related | Guanidine hydrochloride | Naringin | Taurine | Gefitinib | Hydroxychloroquine | 5-Fluorouracil | Curcumin | Stavudine | Tributyrin | L-Ascorbic acid | Paeonol | Sodium 4-phenylbutyrate |
Related Compound Libraries | Inhibitor Library | Bioactive Compound Library | Bioactive Compounds Library Max | Metabolism Compound Library | Kinase Inhibitor Library | Anti-Aging Compound Library | Endocrinology-Hormone Compound Library | Membrane Protein-targeted Compound Library | Orally Active Compound Library | Tyrosine Kinase Inhibitor Library |