AZD-3463
Based on 1 publication(s) in Google Scholar
AZD-3463 (ALK/IGF1R inhibitor) is an orally active ALK/IGF1R inhibitor, with a Ki of 0.75 nM for ALK. AZD3463 induces apoptosis and autophagy in neuroblastoma cells.
For research use only. We do not sell to patients.
- Purity : 99.31%
- CAS No.: 1356962-20-3
- Formula: C24H25ClN6O
- Molecular Weight:448.95
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) AZD-3463
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Biological Activity
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| BaF3 | IC50 |
131.5 nM
Compound: 17; AZD3463
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Cytotoxicity against mouse BaF3 cells expressing human EGFR C797S/T790M/del19 mutant assessed as inhibition of in cell viability measured after 72 hrs by CellTiter-Glo assay
Cytotoxicity against mouse BaF3 cells expressing human EGFR C797S/T790M/del19 mutant assessed as inhibition of in cell viability measured after 72 hrs by CellTiter-Glo assay
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[PMID: 33243531] |
| BaF3 | IC50 |
74.4 nM
Compound: 17; AZD3463
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Cytotoxicity against mouse BaF3 cells expressing human EGFR C797S/del19 mutant assessed as inhibition of in cell viability measured after 72 hrs by CellTiter-Glo assay
Cytotoxicity against mouse BaF3 cells expressing human EGFR C797S/del19 mutant assessed as inhibition of in cell viability measured after 72 hrs by CellTiter-Glo assay
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[PMID: 33243531] |
| IMR-32 | IC50 |
2.8 nM
Compound: 42; AZD3463
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Cytotoxicity against human IMR32 cells
Cytotoxicity against human IMR32 cells
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[PMID: 31419130] |
| PC-9 | IC50 |
253 nM
Compound: AZD3463
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Anticancer activity against human PC-9 cells harboring del19 mutant assessed as inhibition of cell viability incubated for 72 hrs by CellTiter-Glo assay
Anticancer activity against human PC-9 cells harboring del19 mutant assessed as inhibition of cell viability incubated for 72 hrs by CellTiter-Glo assay
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[PMID: 28287083] |
| PC-9 | IC50 |
378.3 nM
Compound: AZD3463
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Anticancer activity against human PC-9 cells harboring T790M/del19 mutant assessed as inhibition of cell viability incubated for 72 hrs by CellTiter-Glo assay
Anticancer activity against human PC-9 cells harboring T790M/del19 mutant assessed as inhibition of cell viability incubated for 72 hrs by CellTiter-Glo assay
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[PMID: 28287083] |
| PC-9 | IC50 |
622.4 nM
Compound: AZD3463
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Anticancer activity against human PC-9 cells harboring C797S/T790M/del19 mutant assessed as inhibition of cell viability incubated for 72 hrs by CellTiter-Glo assay
Anticancer activity against human PC-9 cells harboring C797S/T790M/del19 mutant assessed as inhibition of cell viability incubated for 72 hrs by CellTiter-Glo assay
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[PMID: 28287083] |
| SH-SY5Y | IC50 |
1.7 nM
Compound: 42; AZD3463
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Cytotoxicity against human SH-SY5Y cells
Cytotoxicity against human SH-SY5Y cells
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[PMID: 31419130] |
In Vitro
AZD-3463 (0-50 μM; 72 h) suppresses the viability and proliferation of both wild type and mutant ALK NB cells[1].
AZD-3463 (10 μM; 0-4 h) effectively inhibits ALK-mediated PI3K/AKT/mTOR signaling and induces apoptosis and autophagy in NB cells[1].
AZD-3463 (0-100 nM; 4 h) inhibits FLT3-ITD-mediated activation of AKT, ERK1/2 and p38 in a dose-dependent manner in MOLM-13 and MV4-11 cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:IMR-32, NGP, NB-19, SH-SY5Y, SK-N-AS and LA-N-6 cells
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Concentration:0-50 µM
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Incubation Time:72 h
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Result:Inhibited IMR-32, NGP, NB-19, SH-SY5Y, SK-N-AS and LA-N-6 cells with IC50 values of 2.802, 14.55, 11.94, 1.745, 21.34 and 16.49 µM, respectively.
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Cell Line:IMR-32, NGP , SH-SY5Y and SK-N-AS cells
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Concentration:10 µM
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Incubation Time:0-4 h
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Result:Potently inhibited or totally abolished the phosphorylation of Akt Ser473 and RPS6 Thr235/236.
Induced cleavage of the autophagy marker LC3 A/BΙΙ within four hours.
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Cell Line:MOLM-13 and MV4-11 cells
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Concentration:0-100 nM
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Incubation Time:4 h (pretreat)
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Result:Selectively inhibited FLT3-ITD but not ligand-induced wild-type FLT3.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:5 to 6-week-old female athymic Ncr nude mice (SH-SY5Y and NGP xenograft tumors bearing mice)[1].
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Dosage:15 mg/kg
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Administration:Intraperitoneal injection; once daily for 2 days
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Result:Showed anti-tumor efficacy in both ALK WT and F1174L mutant orthotropic xenograft mouse models of NB.
Chemical Information
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CAS No. 1356962-20-3
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Appearance Solid
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Molecular Weight 448.95
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Formula C24H25ClN6O
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Color Light green to green
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SMILES
ClC(C=NC(NC1=C(OC)C=C(N2CCC(N)CC2)C=C1)=N3)=C3C4=CNC5=C4C=CC=C5
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Synonyms
ALK/IGF1R inhibitor
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (1)
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Journal Impact Factor
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Most Recent
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bioRxiv
PAIRWISE: Deep Learning-based Prediction of Effective Personalized Drug Combinations in Cancer. [Abstract]2024 Nov 6:2024.11.04.621884. PMID: 39574568
Solvent & Solubility
In Vitro:
DMSO : 20 mg/mL (44.55 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2 mg/mL (4.45 mM); Clear solution
This protocol yields a clear solution of ≥ 2 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocols
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Autophagy
Autophagy is a process in which eukaryotic cells use lysosomes to degrade their own cytoplasmic proteins and damaged organelles under the regulation of autophagy related gene (Atg). Microtubule-associated proteins light chain 3 (LC3) is recognized as autophagy marker, which transfers from cytoplasmic LC3 (LC3-I) to membrane type (LC3-II). LC3-II/I ratio could be detected by Western Blot and fluorescence microscopy.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Lysosome and acidic-vesicle live-cell staining
Lysosome and acidic-vesicle live-cell staining detects acidic intracellular compartments by using membrane-permeant acidotropic probes that accumulate in low-pH vesicles, including lysosomes, late endosomes, autolysosomes, and acidic phagosomes. LysoTracker staining is commonly used as an intensity-based readout of acidic lysosomal compartment abundance or enlargement, while acridine orange produces green fluorescence in less concentrated compartments and red fluorescence after concentration-dependent accumulation in acidic vesicular organelles. Loss or reduction of acridine-orange red signal can be used as a readout of lysosomal membrane permeabilization or reduced acidic-vesicle integrity. This protocol is designed for live cultured cells and can be adapted for fluorescence microscopy, high-content imaging, plate-reader readout, or flow cytometry when the selected literature supports the readout. Because these dyes report acidotropic accumulation rather than lysosome identity alone,
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Macroautophagy Solutions
Macroautophagy is a conserved lysosome-dependent degradation pathway in which cytoplasmic material is sequestered into double-membrane autophagosomes and delivered to lysosomes for degradation and recycling. The pathway supports cellular homeostasis during nutrient limitation, organelle stress, protein-aggregate accumulation, infection, differentiation, and tissue remodeling by coupling cargo sequestration, autophagosome maturation, lysosomal fusion, and degradation of cargo-derived macromolecules. The core molecular sequence includes initiation by nutrient- and stress-regulated autophagy machinery, autophagosome nucleation, LC3/ATG8-family conjugation to autophagosomal membranes, cargo selection through receptors such as SQSTM1/p62, autophagosome-lysosome fusion, and lysosomal degradation. LC3 was identified as a mammalian homolog of yeast Atg8 that localizes to autophagosomal membranes after processing, and p62/SQSTM1 was shown to connect ubiquitinated cargo with autophagic degradati
Purity & Documentation
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Data Sheet (281 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Yongfeng Wang, et al. Novel ALK inhibitor AZD3463 inhibits neuroblastoma growth by overcoming crizotinib resistance and inducing apoptosis. Sci Rep. 2016; 6: 19423. [Content Brief]
[2]. Sausan A. Moharram, et al. The ALK inhibitor AZD3463 effectively inhibits growth of sorafenib-resistant acute myeloid leukemia. Blood Cancer J. 2019 Feb; 9(2): 5. [Content Brief]
[3]. Ozates NP, et al. Effects of rapamycin and AZD3463 combination on apoptosis, autophagy, and cell cycle for resistance control in breast cancer. Life Sci. 2021 Jan 1;264:118643. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.2274 mL | 11.1371 mL | 22.2742 mL | 55.6855 mL |
| 5 mM | 0.4455 mL | 2.2274 mL | 4.4548 mL | 11.1371 mL | |
| 10 mM | 0.2227 mL | 1.1137 mL | 2.2274 mL | 5.5685 mL | |
| 15 mM | 0.1485 mL | 0.7425 mL | 1.4849 mL | 3.7124 mL | |
| 20 mM | 0.1114 mL | 0.5569 mL | 1.1137 mL | 2.7843 mL | |
| 25 mM | 0.0891 mL | 0.4455 mL | 0.8910 mL | 2.2274 mL | |
| 30 mM | 0.0742 mL | 0.3712 mL | 0.7425 mL | 1.8562 mL | |
| 40 mM | 0.0557 mL | 0.2784 mL | 0.5569 mL | 1.3921 mL |
AZD-3463 Related Classifications
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