Osimertinib (AZD9291)

Catalog No.S7297 Batch:S729707

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Technical Data

Formula

C28 H33 N7 O2
Molecular Weight 499.61 CAS No. 1421373-65-0
Solubility (25°C)* In vitro DMSO 99 mg/mL (198.15 mM)
Ethanol 99 mg/mL (198.15 mM)
Water Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Osimertinib (AZD9291) 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.
Targets
L858R/T790M EGFR [1]
(LoVo cells)		 Exon 19 deletion EGFR [1]
(LoVo cells)		 WT EGFR [1]
(LoVo cells)
11.44 nM 12.92 nM 493.8 nM
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]
Features Orally bioavailable mutant-selective EGFR inhibitor that has been tested in Phase III clinical trials for treatment of Non-Small Cell Lung Cancer.

Protocol (from reference)

Kinase Assay:

[1]
  • EGFR cellular phosphorylation assay

    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.
Cell Assay:

[3]
  • Cell lines

    PC9 cells

  • Concentrations

    10, 50, & 100 nM

  • Incubation Time

    24 h

  • Method

    Cells were treated with increasing concentrations of osimertinib for 24h.
Animal Study:

[2]
  • Animal Models

    Mice bearing PC9 and H1975 xenograft tumors

  • Dosages

    ~5 mg/kg

  • Administration

    p.o.

Customer Product Validation

, , 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]

Data from [Data independently produced by , , Clin Cancer Res, 2017, 23(12):3139-3149]

Selleck's Osimertinib (AZD9291) has been cited by 410 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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