Osimertinib(Synonyms: 奥希替尼; AZD-9291; Mereletinib)

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Osimertinib (Synonyms: 奥希替尼; AZD-9291; Mereletinib) 纯度: 99.90%

Osimtinib (AZD9291) 是一种共价结合、具有口服活性、不可逆和突变选择性的 EGFR 抑制剂，其有效抑制 L858R (IC50=12 nM) 和 L858R/T790M (IC50=1 nM) EGFR。Osimtinib 解决了肺癌 T790M 突变介导的 EGFR 抑制剂耐药。

Osimertinib(Synonyms: 奥希替尼; AZD-9291; Mereletinib)

Osimertinib Chemical Structure

CAS No. : 1421373-65-0

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10 mM * 1 mL in DMSO ￥715 In-stock
5 mg ￥650 In-stock
10 mg ￥980 In-stock
50 mg ￥1700 In-stock
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200 mg ￥3850 In-stock
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生物活性

Osimertinib (AZD9291) is a covalent, orally active, irreversible, and mutant-selective EGFR inhibitor with an apparent IC50 of 12 nM against L858R and 1 nM against L858R/T790M, respectively. Osimertinib overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer[1].

IC50 & Target[1]

EGFRL858R

12 nM (IC50, Enzyme assays)

EGFRL858R/T790M

1 nM (IC50, Enzyme assays)

体外研究
(In Vitro)

Osimertinib (AZD9291) (0-10 μM; 72 hours) dramatically inhibits cell proliferation with IC50s of 41, 26, 41, and 31 nM, respectively[2].
Osimertinib (0-10 μM; 72 hours) inhibits cell proliferation (Ba/F3 cells harboring a T790M mutation, exon 19del+T790M, or L858R+T790M) with IC50s of 6, 7, and 74 nM, respectively[2].
Osimertinib (0-10 μM; 72 hours) inhibits Ba/F3 cells harboring EGFR exon 20 insertion mutations (IC50 ranging from 16 to 701 nM for A763_Y764insFQEA (FQEA), Y764_V765insHH (HH), A767_V769dupASV (ASV), and D770_N771insNPG (NPG) cells)[2].
Osimertinib shows high levels of phenotype potency in both sensitizing-mutant (mean IC50 of 8 nM in PC-9) and T790M (mean IC50s of 11 and 40 nM in H1975 and PC-9VanR respectively) EGFR cell lines. Osimertinib has much less activity towards wild-type EGFR (mean IC50s of 650 and 461 nM in Calu3 and H2073 respectively)[1].
Osimertinib (0.1 μM; 48 hours) induces apoptosis in Ba/F3 cells (apoptosis rates of 40.9% and 90% in EGFR exon 19del+T790M, EGFR L858R+T790M respectively) [2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay[2]

Cell Line: Ba/F3 cells (harboring a T790M mutation, exon 19del+T790M, or L858R+T790M)
Concentration: 0.0001, 0.001, 0.01, 0.1, 1, 10 μM
Incubation Time: 72 hours
Result: Inhibited cell proliferation (IC50s=6, 7, 74 nM, respectively)

Cell Proliferation Assay[2]

Cell Line: PC-9, H3255, PC-9ER, and H1975 cells
Concentration: 0.0001, 0.001, 0.01, 0.1, 1, 10 μM
Incubation Time: 72 hours
Result: Dramatically inhibited cell proliferation (IC50s=41, 26, 41, 31 nM, respectively)

Cell Proliferation Assay[2]

Cell Line: Ba/F3 cells (harboring EGFR exon 20 insertion mutations: FQEA, HH, ASV, NPG )
Concentration: 0.0001, 0.001, 0.01, 0.1, 1, 10 μM
Incubation Time: 72 hours
Result: Inhibited cell proliferation (IC50s=16, 701, 230, 38 nM, respectively)

Apoptosis Analysis[2]

Cell Line: Ba/F3 cells (harboring EGFR exon 19del+T790M or EGFR L858R+T790M)
Concentration: 0.1 μM
Incubation Time: 48 hours
Result: Induced apoptosis with the rates of 40.9% and 90% in EGFR T790M positive mutations cells, respectively.

体内研究
(In Vivo)

Osimertinib (0.1-25 mg/kg; p.o.; daily for 14 days) induces significant dose-dependent regression in both PC-9 (ex19del) and H1975 (L858R/T790M) tumor xenograft models[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: PC-9 (ex19del) and H1975 (L858R/T790M) tumor xenograft models[1]
Dosage: 0.1-10 mg/kg (PC-9 xenograft models); 0.5- 25 mg/kg (H1975 xenograft models)
Administration: p.o.; daily for 14 days
Result: Induced significant dose-dependent regression in both PC-9 (ex19del) and H1975 (L858R/T790M) tumor xenograft models.

Clinical Trial

分子量

499.61

Formula

C28H33N7O2
CAS 号

1421373-65-0
中文名称

奥斯替尼；奥希替尼
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 125 mg/mL (250.20 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.0016 mL 10.0078 mL 20.0156 mL
5 mM 0.4003 mL 2.0016 mL 4.0031 mL
10 mM 0.2002 mL 1.0008 mL 2.0016 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂： 0.5%HPMC  1%Tween80

    Solubility: 5 mg/mL (10.01 mM); Suspened solution; Need ultrasonic and warming and heat to 60°C

  • 2.

    请依序添加每种溶剂： 10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (5.00 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.00 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

  • 3.

    请依序添加每种溶剂： 5% DMSO    40% PEG300    5% Tween-80    50% saline

    Solubility: ≥ 2.5 mg/mL (5.00 mM); Clear solution

  • 4.

    请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.08 mg/mL (4.16 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (4.16 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Cross DA, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep;4(9):1046-61.

    [2]. Hirano T, et al. Pharmacological and Structural Characterizations of Naquotinib, a Novel Third-Generation EGFR Tyrosine Kinase Inhibitor, in EGFR-Mutated Non-Small Cell Lung Cancer. Mol Cancer Ther. 2018 Apr;17(4):740-750.

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