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Naquotinib(ASP8273) EGFR inhibitor

Name: Naquotinib(ASP8273)
Brand: Selleck Chemicals
SKU: S8412
Availability: InStock
Rating: 5 (1 reviews)

Cat.No.S8412

Naquotinib (ASP8273) is an orally available, irreversible, mutant-selective, epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity.

Chemical Structure

Molecular Weight: 562.71

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

Quality Control

Batch: S841201 Ethanol]100 mg/mL]false]DMSO]52 mg/mL]false]Water]Insoluble]false Purity: 99.43%

99.43

Related Targets	VEGFR JAK PDGFR FGFR Src FLT3 HER2 Bcr-Abl HIF BTK ALK Syk FAK VDA
Related Products	AG-490 AG-1478 Canertinib (CI-1033) Rociletinib (CO-1686) WZ4002 Genistein Poziotinib PD153035 PD153035 HCl Allitinib tosylate AEE788 (NVP-AEE788) Pelitinib (EKB-569) Canertinib dihydrochloride Varlitinib Icotinib (BPI-2009H) Nazartinib (EGF816) NSC228155 PD168393 Olmutinib (BI 1482694) Zorifertinib (AZD3759) AZ5104 Lazertinib CL-387785 (EKI-785) TAK-285 Daphnetin Pyrotinib dimaleate Alflutinib (Furmonertinib) mesylate EGFR Inhibitor Chrysophanic Acid Norcantharidin

Chemical Information, Storage & Stability

Molecular Weight	562.71	Formula	C₃₀H₄₂N₈O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1448232-80-1	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CCC1=C(N=C(C(=N1)C(=O)N)NC2=CC=C(C=C2)N3CCC(CC3)N4CCN(CC4)C)OC5CCN(C5)C(=O)C=C

Solubility

In vitro
Batch:

Ethanol : 100 mg/mL

DMSO : 52 mg/mL ( (92.4 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 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.	2.6mg/ml (4.62mM)	Taking the 1 mL working solution as an example, add 50 μL of 52 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.	0.175mg/ml (0.31mM)	Taking the 1 mL working solution as an example, add 50 μL of 3.5 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	mutant EGFR ^[1]
In vitro	Naquotinib (ASP8273) is a small-molecule irreversible TKI inhibitor that inhibits the kinase activity of EGFR mutations including T790M, with limited activity against EGFR wild-type (WT) NSCLC. In the in vitro enzymatic and cell-based assays, this compound is evaluated against EGFR mutants (L858R, exon 19 deletion, L858R/T790M, and del19/T790M) and WT EGFR. It is found by mass spectrometry to covalently bind to a mutant EGFR (L858R/T790M) via cysteine residue 797 in the kinase domain of EGFR with long-lasting inhibition of EGFR phosphorylation for 24 h. In the NSCLC cell lines harboring the above EGFR mutations, it has IC50 values of 8-33 nM toward EGFR mutants, more potently than that of WT EGFR (IC50 value of 230 nM). It is further shown to suppress the signaling pathway through ERK and Akt. This compound even shows activity in mutant EGFR cell line which is resistant to other EGFR TKIs including AZD9291 and CO-1686^[1]^[2].
In vivo	In mouse xenograft studies, S8412 induces tumor regression in NCI-H1975 (L858R/T790M), HCC827 (del ex19) and PC-9 (del ex19) xenograft models by repeated oral dosing in a dose-dependent manner. Dosing schedules do not affect the efficacy of ASP8273. In HCC827 and NCI-H1975 xenograft models, S8412 induces tumor regression at 10, 30 and 100mg/kg without affecting body weight. S8412 also produces tumor growth inhibition from 10mg/kg in the NSCLC patient derived tumor xenograft, LU1868 which express T790M/L858R. On the other hand, S8412 does not produce significant tumor growth inhibition at 10 and 30mg/kg in A431 xenograft model^[1]^[2].
References	http://cancerres.aacrjournals.org/content/74/19_Supplement/1728.short http://cancerres.aacrjournals.org/content/75/15_Supplement/2586.short

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03082300	Terminated	Non-small Cell Lung Cancer (NSCLC)\|Epidermal Growth Factor Receptor (EGFR) Mutations	Astellas Pharma Global Development Inc.\|Astellas Pharma Inc	March 24 2017	Phase 1
NCT02674555	Withdrawn	Epidermal Growth Factor Receptor (EGFR) Mutations\|Solid Tumors	Astellas Pharma Global Development Inc.\|Astellas Pharma Inc	November 15 2016	Phase 1
NCT02500927	Terminated	EGFR-TKI-naïve Patients With NSCLC Harboring EGFR Activating Mutations	Astellas Pharma Inc	June 25 2015	Phase 2
NCT02113813	Completed	Non-Small-Cell Lung Cancer (NSCLC)\|Epidermal Growth Factor Receptor Mutations	Astellas Pharma Global Development Inc.\|Astellas Pharma Inc	April 9 2014	Phase 1
NCT02192697	Terminated	Non-small Cell Lung Cancer	Astellas Pharma Inc	January 23 2014	Phase 1\|Phase 2

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