Osimertinib (AZD9291)

製品コードS7297 バッチS729710

印刷

化学情報

Synonyms

Mereletinib

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₈ H₃₃ N₇ O₂

分子量

499.61

CAS No.

1421373-65-0

Solubility (25°C)*

体外

DMSO (warmed with 50ºC water bath)

100 mg/mL (200.15 mM)

Ethanol (warmed with 50ºC water bath)

33 mg/mL (66.05 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution	5% DMSO 1 95% Corn oil	0.8mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 16 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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	7.5mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 150 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 make it clear; 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.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Osimertinib (AZD9291, Mereletinib) is an oral, irreversible, and mutant-selective EGFR inhibitor with IC50 of 12.92, 11.44 and 493.8 nM for Exon 19 deletion EGFR, L858R/T790M EGFR, and WT EGFR in LoVo cells, respectively. Phase 3.
in vitro	AZD9291 shows significantly more potent inhibition of proliferation in mutant EGFR cell lines compared to wild-type in vitro. ^[2]
in vivo	AZD9291(5mg/kg p.o.) causes profound regression of tumors across EGFRm+ (PC9) and EGFRm+/T790M (H1975) tumor models with profound inhibition of EGFR phosphorylation and key downstream signaling pathways such as AKT and ERK in vivo. ^[2]
特徴	Orally bioavailable mutant-selective EGFR inhibitor that has been tested in Phase III clinical trials for treatment of Non-Small Cell Lung Cancer.

プロトコル(参考用のみ)

キナーゼアッセイ	EGFR cellular phosphorylation assay
キナーゼアッセイ	Cells are seeded (10000 cells/well) in growth medium in Corning black, clear- bottomed 384-well plates and incubated at 37°C with 5% CO₂ overnight. Cells are acoustically dosed using an Echo 555, with compounds serially diluted in 100% DMSO. Plates are incubated for a further 2h, then following aspiration of medium, 40μL lx lysis buffer is added to each well. Greiner black high bind 384-well plates are coated with capture antibody and then blocked with 3% BSA. Following removal of block, 15μL of lysate are transferred to the Greiner black high bind 384-well plates and incubated for 2 hours. Following aspiration and washing of the plates with PBS, 20μL, of detection antibody were added and incubated for 2 hours. Following aspiration and washing of the plates with PBS, 20μL of QuantaBlu fluorogenic peroxidase substrate are added and incubated for 1 hour. 20μL QuantaBlu stop solution are added to plates and fluorescence read on an Envision plate reader using Excitation 352nm wavelength and emission 460nm wavelength. The data obtained with each compound is exported into a suitable software package to perform curve fitting analysis. From this data an IC50 value is determined by calculation of the concentration of compound that is required to give a 50% effect.
細胞アッセイ	細胞株	PC9 cells
	濃度	10, 50, & 100 nM
	反応時間	24 h
	実験の流れ	Cells were treated with increasing concentrations of osimertinib for 24h.
動物実験	動物モデル	Mice bearing PC9 and H1975 xenograft tumors
	投薬量	~5 mg/kg
	投与方法	p.o.

参考

カスタマーフィードバック

: , , Cancer Res, 2017, 77(8):2078-2089

: Data from [Data independently produced by , , J Thorac Oncol, 2018, 13(7):915-925]

: Data from [Data independently produced by , , J Thorac Oncol, 2017, 12(5):884-889]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Targeting of vulnerabilities of drug-tolerant persisters identified through functional genetics delays tumor relapse [ Cell Rep Med, 2024, 5(3):101471]	PubMed: 38508142
TP53 gain-of-function mutations promote osimertinib resistance via TNF-α-NF-κB signaling in EGFR-mutated lung cancer [ NPJ Precis Oncol, 2024, 8(1):60]	PubMed: 38431700
A destabilizing Y891D mutation in activated EGFR impairs sensitivity to kinase inhibition [ NPJ Precis Oncol, 2024, 8(1):3]	PubMed: 38182677
Genetic alterations predict poor efficacy, outcomes and resistance to second-line osimertinib treatment in non-small cell lung cancer [ Am J Cancer Res, 2024, 14(1):33-51]	PubMed: 38323283
The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer [ Cancers (Basel), 2024, 16(6)1170]	PubMed: 38539505
Non-small cell lung cancer cells with uncommon EGFR exon 19delins variants respond poorly to third-generation EGFR inhibitors [ Transl Oncol, 2024, 39:101834]	PubMed: 38006760
Aberrant m5C hypermethylation mediates intrinsic resistance to gefitinib through NSUN2/YBX1/QSOX1 axis in EGFR-mutant non-small-cell lung cancer [ Mol Cancer, 2023, 22(1):81]	PubMed: 37161388
H3K4me3 remodeling induced acquired resistance through O-GlcNAc transferase [ Drug Resist Updat, 2023, 71:100993]	PubMed: 37639774
MUC1-C Is a Common Driver of Acquired Osimertinib Resistance in NSCLC [ J Thorac Oncol, 2023, 10.1016/j.jtho.2023.10.017]	PubMed: 37924972
Secondary Mutations of the EGFR Gene That Confer Resistance to Mobocertinib in EGFR Exon 20 Insertion [ J Thorac Oncol, 2023, S1556-0864(23)00797-9]	PubMed: 37666482

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。