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AZD3463 ALK inhibitor

Name: AZD3463
Brand: Selleck Chemicals
SKU: S7106
Availability: InStock
Rating: 5 (8 reviews)

Cat.No.S7106

AZD3463 is a novel orally bioavailable ALK inhibitor with K_i of 0.75 nM, which also inhibits IGF1R with equivalent potency. This compound suppresses cell viability by inducing both cell apoptosis and autophagy.

Chemical Structure

Molecular Weight: 448.95

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: S710601 DMSO]6 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.98%

99.98

Related Targets	EGFR VEGFR PDGFR FGFR c-Met Src FLT3 HER2 c-Kit Bcr-Abl MEK BTK IGF-1R Trk receptor Syk Axl CSF-1R c-RET FAK Mertk Tie-2 DYRK Tyro3 Ephrin receptor ROS1 Pyk2 RON DDR ACK Fer kinase
Related Products	TAE684 (NVP-TAE684) GSK1838705A Repotrectinib (TPX-0005) AP26113-analog (ALK-IN-1) Ensartinib dihydrochloride ASP3026 HG-14-10-04 X-376 ALK inhibitor 1 TL13-112 APG-2449 Envonalkib NVL-655 Anti-ACVR1 / ALK-2 (DS-6016a) Iruplinalkib MS4078 Belizatinib (TSR-011) Zotizalkib Zilurgisertib fumarate Itacnosertib (TP-0184) Ascrinvacumab (Anti-ACVRL1 / ALK-1) ZX-29

Chemical Information, Storage & Stability

Molecular Weight	448.95	Formula	C₂₄H₂₅ClN₆O	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1356962-20-3	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	COC1=C(C=CC(=C1)N2CCC(CC2)N)NC3=NC=C(C(=N3)C4=CNC5=CC=CC=C54)Cl

Solubility

In vitro
Batch:

DMSO : 6 mg/mL (13.36 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.3mg/ml (0.67mM)	Taking the 1 mL working solution as an example, add 50 μL of 6 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.043mg/ml (0.10mM)	Taking the 1 mL working solution as an example, add 50 μL of 0.86 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	IGF-1R ^[2] ALK ^[1] 0.75 nM(Ki)
In vitro	AZD3463 is potent in ALK-driven preclinical models and in a variety of crizotinib-resistant models. This compound inhibits ALK in cells as demonstrated by its ability to decrease ALK autophosphorylation in tumor cell lines containing ALK fusions including DEL (ALCL NPM-ALK), H3122 (NSCLC EML4-ALK) and H2228 (NSCLC EML4-ALK). Inhibition of ALK is associated with perturbations in downstream signaling including ERK, AKT and STAT3 pathways leading to preferential inhibition of proliferation in the ALK fusion containing cell lines in vitro. It retains good activity against a number of clinically relevant crizotinib resistant mutations including the gatekeeper mutant L1196M where equivalent potency to wild type ALK is observed in vitro and in vivo in EML4-ALK containing BAF3 cell lines. To further assess the potential ability of this chemical to overcome additional resistance mechanisms, antiproliferative activity is assessed in multiple crizotinib resistant cell lines independently derived in vitro from H3122 cells as well as a patient derived crizotinib relapsed model. These resistant cell lines contain multiple resistance mechanisms including the L1196M gatekeeper and T115Ins mutations, ALK amplification and/or secondary drivers including EGFR and IGF1R. This compound retains antiproliferative potency within 4 fold of parental H3122 cells for 10 out of 12 of these acquired resistance models in vitro. ^[1]
In vivo	AZD3463 also demonstrates the ability to dose dependently inhibit pALK in xenograft tumors in vivo resulting in stasis (H3122) or regression (DEL, H2228). ^[1]
References	[1] http://cancerres.aacrjournals.org/content/73/8_Supplement/919 [2] https://www.nature.com/articles/s41598-017-14289-w

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