| 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 | In vivo, AZD-3463 is equally effective against both the mutated L1196M and the wild-type ALK. When acting on transplanted tumors in vivo, AZD-3463 dose-dependently inhibits pALK, leading to the stagnation (H3122) or reduction (DEL, H2228) of tumor volume. |
| In vivo | In various in vitro models resistant to Crizotinib, AZD3463 exhibits antiproliferative efficacy against five out of six cell lines, with a potency four times greater than that of the parent H3122 cells. AZD3463 is effective across tumor cell lines with ALK fusion, including DEL (ALCL NPM-ALK), H2228 (NSCLC EML4-ALK), and H3122 (NSCLC EML4-ALK), by inhibiting ALK and reducing its autophosphorylation. |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 23 mg/mL (51.23 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (4.45 mM), Sonication is recommended.
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| Keywords | tyrosine | resistance | receptor | PI3K/AKT/mTOR. pathway | neuroblastoma | kinase | Inhibitor | inhibit | IGF-1R | IGF1R | crizotinib | Cluster of differentiation 246 | CD246 | AZD-3463 | AZD3463 | AZD 3463 | Autophagy | Apoptosis | Anaplastic lymphoma kinase (ALK) | Anaplastic lymphoma kinase | ALK tyrosine kinase receptor | ALK |
| Inhibitors Related | Stavudine | Aceglutamide | Hemin | Urea | Tamoxifen | Guanidine hydrochloride | Hydroxychloroquine | Metronidazole | Formamide | Paeonol | Naringin | Alginic acid |
| Related Compound Libraries | Anti-Pancreatic Cancer Compound Library | Bioactive Compound Library | Membrane Protein-targeted Compound Library | Kinase Inhibitor Library | Tyrosine Kinase Inhibitor Library | Autophagy Compound Library | Angiogenesis related Compound Library | Inhibitor Library | Stem Cell Differentiation Compound Library | NO PAINS Compound Library | Anti-Aging Compound Library | Bioactive Compounds Library Max |
United States
