Osimertinib (AZD9291)

Catalog No.S7297 Batch:S729708

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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 100 mg/mL (200.15 mM)
Ethanol 100 mg/mL (200.15 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 440 publications

Branched-chain amino acid transaminase 1 confers EGFR-TKI resistance through epigenetic glycolytic activation [ Signal Transduct Target Ther, 2024, 9(1):216] PubMed: 39143065
Tet methylcytosine dioxygenase 2 (TET2) deficiency elicits EGFR-TKI (tyrosine kinase inhibitors) resistance in non-small cell lung cancer [ Signal Transduct Target Ther, 2024, 9(1):65] PubMed: 38461173
Base editing screens define the genetic landscape of cancer drug resistance mechanisms [ Nat Genet, 2024, 10.1038/s41588-024-01948-8] PubMed: 39424923
Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer [ Nat Commun, 2024, 15(1):3741] PubMed: 38702301
Comprehensive mutational scanning of EGFR reveals TKI sensitivities of extracellular domain mutants [ Nat Commun, 2024, 15(1):2742] PubMed: 38548752
RAB22A sorts epithelial growth factor receptor (EGFR) from early endosomes to recycling endosomes for microvesicles release [ J Extracell Vesicles, 2024, 13(7):e12494] PubMed: 39051763
Targeting of vulnerabilities of drug-tolerant persisters identified through functional genetics delays tumor relapse [ Cell Rep Med, 2024, 5(3):101471] PubMed: 38508142
PIM1 kinase promotes EMT-associated osimertinib resistance via regulating GSK3β signaling pathway in EGFR-mutant non-small cell lung cancer [ Cell Death Dis, 2024, 15(9):644] PubMed: 39227379
GLI1 confers resistance to PARP inhibitors by activating the DNA damage repair pathway [ Oncogene, 2024, 10.1038/s41388-024-03105-1] PubMed: 39095584
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

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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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