1. JAK/STAT Signaling
    Protein Tyrosine Kinase/RTK
  2. EGFR

AZD-9291 (Synonyms: Osimertinib; Mereletinib)

Cat. No.: HY-15772 Purity: 99.95%
Data Sheet SDS Handling Instructions

AZD-9291 is a third generation irreversible EGFR tyrosine kinase inhibitor with selectivity against mutant versus wild-type forms of EGFR, shows an apparent IC50 of 12 nM against L858R and 1 nM against L858R/T790M in EGFR recombinant enzyme assay.

For research use only. We do not sell to patients.
AZD-9291 Chemical Structure

AZD-9291 Chemical Structure

CAS No. : 1421373-65-0

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Customer Review

Other Forms of AZD-9291:

    AZD-9291 purchased from MCE. Usage Cited in: Oncotarget. 2015 Oct 13;6(31):31313-22.

    Effect of Ibrutinib on EGFR wt/mutant NSCLCs. Ibrutinib effects on wt EGFR and mutant EGFR- mediated signaling pathways. The results demonstrate that Ibrutinib potently inhibits both EGFR wt/mutant auto-phosphorylation at Y1068.

    AZD-9291 purchased from MCE. Usage Cited in: Oncotarget. 2015 Oct 13;6(31):31313-22.

    Effect of Ibrutinib, WZ4002, AZD9291 and CO1686 on EGFR phosphorylation of tyrosines 1068 and 1173 in EGFR-dependent cancer cell lines.

    AZD-9291 purchased from MCE. Usage Cited in: Oncotarget. 2016 Oct 25;7(43):69760-69769.

    Ibrutinib and WZ4002 inhibitory effects on EGFRY1068 auto-phosphorylation in the H1975 cell line at different time points by removal of drug after 4 h pretreatment

    AZD-9291 purchased from MCE. Usage Cited in: Oncotarget. 2017 Mar 14;8(11):18359-18372.

    In all of the cell lines tested, AZD9291 significantly affects the phosphorylation of eIF4E, which presumably is due to its strong inhibitory activity against MNK2 kinase.

    AZD-9291 purchased from MCE. Usage Cited in: Oncotarget. 2017 Mar 14;8(11):18359-18372.

    In all of the cell lines tested, AZD9291 significantly affects the phosphorylation of eIF4E, which presumably is due to its strong inhibitory activity against MNK2 kinase.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    AZD-9291 is a third generation irreversible EGFR tyrosine kinase inhibitor with selectivity against mutant versus wild-type forms of EGFR, shows an apparent IC50 of 12 nM against L858R and 1 nM against L858R/T790M in EGFR recombinant enzyme assay.

    IC50 & Target

    IC50: 1 nM (EGFRL858R/T790M), 12 nM (EGFRL858R)[1]

    In Vitro

    AZD-9291 (AZD9291) shows similar potency to early generation tyrosine kinase inhibitor (TKIs) in inhibiting EGFR phosphorylation in EGFR cells harboring sensitising EGFR mutants including PC-9 (ex19del), H3255 (L858R) and H1650 (ex19del), with mean IC50 values ranging from 13 to 54 nM for AZD-9291. AZD-9291 also potently inhibits phosphorylation of EGFR in T790M mutant cell lines (H1975 (L858R/T790M), PC-9VanR (ex19del/T790M), with mean IC50 potency less than 15 nM[1].

    In Vivo

    The tumor-bearing mice are treated with AZD-9291 (5 mg/kg/day) for one to two weeks. Within days of treatment, 5 of 5 C/L858R mice displays nearly 80% reduction in tumor volume by magnetic resonance imaging MRI after therapy with AZD-9291, while 5 of 5 mice treated with vehicle shows tumor growth[1]. AZD-9291 demonstrates improved rat PK, reduced hERG affinity, and improved IGF1R margins relative to the previously described compounds, and so this compound is selected for further investigation. AZD-9291 also offers an additional degree of broader chemical and profile diversity when compared to the previously described lead compounds. Upon dosing AZD-9291 in three efficacy models, The comparable efficacy is observed at relatively low doses (10 mg/kg per day). The excellent efficacy is also observed when AZD-9291 is dosed at 5 mg/kg per day[2].

    Clinical Trial
    NCT Number Sponsor Condition Start Date Phase
    NCT02771314 Hellenic Oncology Research Group Non Small Cell Lung Cancer June 2016 Phase 2
    NCT02736513 Rabin Medical Center Lung Cancer May 2016 Phase 2
    NCT02972333 Shandong Cancer Hospital and Institute|AstraZeneca EGFR-TKI Resistant Mutation|Nonsmall Cell Lung Cancer|AZD9291|Brain Metastases December 2016 Phase 3
    NCT02511106 AstraZeneca|Parexel Stage IB-IIIA Non-small Cell Lung Carcinoma October 21, 2015 Phase 3
    NCT02157883 AstraZeneca Advanced Non Small Cell Lung Cancer|Advanced (Inoperable) Non Small Cell Lung Cancer November 6, 2014 Phase 1
    NCT02811354 National University Hospital, Singapore|AstraZeneca|Singapore Clinical Research Institute Carcinoma, Non-Small-Cell Lung February 24, 2017 Phase 2
    NCT02096679 AstraZeneca Healthy Volunteers May 2014 Phase 1
    NCT02151981 AstraZeneca Anticancer Treatment August 4, 2014 Phase 3
    NCT02197247 AstraZeneca Non Small Cell Lung Cancer December 4, 2014 Phase 1
    NCT02491944 AstraZeneca Oncology July 2015 Phase 1
    NCT02454933 AstraZeneca Locally Advanced or Metastatic EGFR T790M+ NSCLC July 15, 2015 Phase 3
    NCT02224053 AstraZeneca Healthy Volunteer September 2014 Phase 1
    NCT02474355 AstraZeneca|Parexel Lung Cancer September 18, 2015 Phase 3
    NCT02094261 AstraZeneca Non Small Cell Lung Cancer May 20, 2014 Phase 2
    NCT01802632 AstraZeneca Advanced Non Small Cell Lung Cancer|Advanced (Inoperable) Non Small Cell Lung Cancer March 4, 2013 Phase 1|Phase 2
    NCT02442349 AstraZeneca Non-Small Cell Lung Cancer June 2015 Phase 2
    NCT02163733 AstraZeneca Advanced Non Small Cell Lung Cancer|Advanced (Inoperable) Non Small Cell Lung Cancer November 14, 2014 Phase 1
    NCT02317016 AstraZeneca Non Small Cell Lung Cancer March 10, 2015 Phase 1
    NCT02161770 AstraZeneca Solid Tumours December 22, 2014 Phase 1
    NCT02197234 AstraZeneca Non Small Cell Lung Cancer December 22, 2014 Phase 1
    NCT02228369 AstraZeneca EGFR Mutation Positive Advanced Non Small Cell Lung Cancer November 5, 2014 Phase 1
    NCT02451852 AstraZeneca EGFR T790M Mutation Positive NSCLC
    NCT02296125 AstraZeneca|Parexel Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer December 3, 2014 Phase 3
    NCT01951599 AstraZeneca Healthy Volunteers October 9, 2013 Phase 1
    NCT02143466 AstraZeneca Advanced Non Small Cell Lung Cancer August 5, 2014 Phase 1
    NCT02504346 Oslo University Hospital|AstraZeneca Lung Cancer|Targeted Therapy August 2015 Phase 2
    NCT02923947 AstraZeneca|Quintiles, Inc. Solid Tumours May 4, 2017 Phase 1
    NCT02997501 AstraZeneca|TigerMed Lung Cancer December 23, 2016 Phase 3
    NCT02179671 AstraZeneca|Quintiles, Inc. Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV) July 2014 Phase 2
    NCT02529995 AstraZeneca Carcinoma, Non-Small-Cell Lung With EGFR Mutation Positive August 24, 2015 Phase 1
    NCT02664935 University of Birmingham|Cancer Research UK|AstraZeneca|Pfizer|Experimental Cancer Medicine Centre Network Non-Small Cell Lung Cancer|Carcinoma, Squamous Cell|Adenocarcinoma March 2015 Phase 2
    NCT02771314 Hellenic Oncology Research Group Non Small Cell Lung Cancer June 2016 Phase 2
    NCT02736513 Rabin Medical Center Lung Cancer May 2016 Phase 2
    NCT02972333 Shandong Cancer Hospital and Institute|AstraZeneca EGFR-TKI Resistant Mutation|Nonsmall Cell Lung Cancer|AZD9291|Brain Metastases December 2016 Phase 3
    NCT02511106 AstraZeneca|Parexel Stage IB-IIIA Non-small Cell Lung Carcinoma October 21, 2015 Phase 3
    NCT02157883 AstraZeneca Advanced Non Small Cell Lung Cancer|Advanced (Inoperable) Non Small Cell Lung Cancer November 6, 2014 Phase 1
    NCT02811354 National University Hospital, Singapore|AstraZeneca|Singapore Clinical Research Institute Carcinoma, Non-Small-Cell Lung February 24, 2017 Phase 2
    NCT02096679 AstraZeneca Healthy Volunteers May 2014 Phase 1
    NCT02151981 AstraZeneca Anticancer Treatment August 4, 2014 Phase 3
    NCT02197247 AstraZeneca Non Small Cell Lung Cancer December 4, 2014 Phase 1
    NCT02491944 AstraZeneca Oncology July 2015 Phase 1
    NCT02454933 AstraZeneca Locally Advanced or Metastatic EGFR T790M+ NSCLC July 15, 2015 Phase 3
    NCT02224053 AstraZeneca Healthy Volunteer September 2014 Phase 1
    NCT02474355 AstraZeneca|Parexel Lung Cancer September 18, 2015 Phase 3
    NCT02094261 AstraZeneca Non Small Cell Lung Cancer May 20, 2014 Phase 2
    NCT01802632 AstraZeneca Advanced Non Small Cell Lung Cancer|Advanced (Inoperable) Non Small Cell Lung Cancer March 4, 2013 Phase 1|Phase 2
    NCT02442349 AstraZeneca Non-Small Cell Lung Cancer June 2015 Phase 2
    NCT02163733 AstraZeneca Advanced Non Small Cell Lung Cancer|Advanced (Inoperable) Non Small Cell Lung Cancer November 14, 2014 Phase 1
    NCT02317016 AstraZeneca Non Small Cell Lung Cancer March 10, 2015 Phase 1
    NCT02161770 AstraZeneca Solid Tumours December 22, 2014 Phase 1
    NCT02197234 AstraZeneca Non Small Cell Lung Cancer December 22, 2014 Phase 1
    NCT02228369 AstraZeneca EGFR Mutation Positive Advanced Non Small Cell Lung Cancer November 5, 2014 Phase 1
    NCT02451852 AstraZeneca EGFR T790M Mutation Positive NSCLC
    NCT02296125 AstraZeneca|Parexel Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer December 3, 2014 Phase 3
    NCT01951599 AstraZeneca Healthy Volunteers October 9, 2013 Phase 1
    NCT02143466 AstraZeneca Advanced Non Small Cell Lung Cancer August 5, 2014 Phase 1
    NCT02504346 Oslo University Hospital|AstraZeneca Lung Cancer|Targeted Therapy August 2015 Phase 2
    NCT02923947 AstraZeneca|Quintiles, Inc. Solid Tumours May 4, 2017 Phase 1
    NCT02997501 AstraZeneca|TigerMed Lung Cancer December 23, 2016 Phase 3
    NCT02179671 AstraZeneca|Quintiles, Inc. Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV) July 2014 Phase 2
    NCT02529995 AstraZeneca Carcinoma, Non-Small-Cell Lung With EGFR Mutation Positive August 24, 2015 Phase 1
    NCT02664935 University of Birmingham|Cancer Research UK|AstraZeneca|Pfizer|Experimental Cancer Medicine Centre Network Non-Small Cell Lung Cancer|Carcinoma, Squamous Cell|Adenocarcinoma March 2015 Phase 2
    NCT02841579 MedSIR|AstraZeneca Non-Small Cell Lung Cancer August 2016 Phase 2
    NCT02769286 Chonnam National University Hospital Lung Neoplasms|EGFR Gene Mutations August 2016 Phase 2
    NCT02803203 Memorial Sloan Kettering Cancer Center|AstraZeneca|Genentech, Inc. Non-small Cell Lung Cancer|EGFR-mutant Lung Cancers June 29, 2016 Phase 1|Phase 2
    NCT03122717 Dana-Farber Cancer Institute|AstraZeneca Non-Small Cell Lung Cancer April 2017 Phase 1
    NCT02856893 European Organisation for Research and Treatment of Cancer - EORTC|AstraZeneca NSCLC March 2017 Phase 2
    NCT03133546 European Thoracic Oncology Platform|AstraZeneca|Hoffmann-La Roche Non Small Cell Lung Cancer Metastatic May 2017 Phase 2
    NCT03191149 National Cancer Institute (NCI) EGFR Exon 20 Insertion Mutation|Recurrent Non-Small Cell Lung Carcinoma|Stage IIIB Non-Small Cell Lung Cancer AJCC v7|Stage IV Non-Small Cell Lung Cancer AJCC v7 May 11, 2018 Phase 2
    NCT02759835 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Lung Adenocarcinoma|Lung Neoplasms April 4, 2016 Phase 2
    NCT02496663 National Cancer Institute (NCI) EGFR Exon 19 Deletion Mutation|EGFR NP_005219.2:p.G719X|EGFR NP_005219.2:p.L858R|EGFR NP_005219.2:p.L861Q|EGFR T790M Mutation Negative|Recurrent Non-Small Cell Lung Carcinoma|Stage IV Non-Small Cell Lung Cancer AJCC v7 March 24, 2016 Phase 1
    NCT02954523 Giuseppe Giaccone|AstraZeneca|Bristol-Myers Squibb|Walter Reed National Military Medical Center|Hackensack University Medical Center|Georgetown University EGFR Gene Mutation|Nonsmall Cell Lung Cancer October 2016 Phase 1|Phase 2
    NCT02917993 Incyte Corporation|AstraZeneca Non-Small Cell Lung Cancer November 2016 Phase 1|Phase 2
    NCT02789345 Eli Lilly and Company|AstraZeneca Non-small Cell Lung Cancer October 24, 2016 Phase 1
    NCT02971501 National Cancer Institute (NCI) EGFR Activating Mutation|EGFR NP_005219.2:p.T790M|Metastatic Malignant Neoplasm in the Brain|Non-Small Cell Lung Carcinoma|Recurrent Non-Small Cell Lung Carcinoma December 29, 2017 Phase 2
    NCT02520778 National Cancer Institute (NCI) EGFR Activating Mutation|Recurrent Non-Small Cell Lung Carcinoma|Stage III Non-Small Cell Lung Cancer AJCC v7|Stage IIIA Non-Small Cell Lung Cancer AJCC v7|Stage IIIB Non-Small Cell Lung Cancer AJCC v7|Stage IV Non-Small Cell Lung Cancer AJCC v7 March 31, 2016 Phase 1
    NCT02959749 Qingdao Central Hospital Progression Free Survival August 2015 Phase 2|Phase 3
    NCT03133234 AstraZeneca T790M Positive NSCLC Patients May 23, 2017
    NCT02503722 National Cancer Institute (NCI) Recurrent Non-Small Cell Lung Carcinoma|Stage IIIA Non-Small Cell Lung Cancer AJCC v7|Stage IIIB Non-Small Cell Lung Cancer AJCC v7|Stage IV Non-Small Cell Lung Cancer AJCC v7 October 13, 2016 Phase 1
    NCT03219970 AstraZeneca EGFR and T790M Mutation Positive NSCLC Patients October 31, 2017
    NCT03050411 Peking University Third Hospital Nonsmall Cell Lung Cancer May 2016 Phase 1
    NCT02465060 National Cancer Institute (NCI) Advanced Malignant Solid Neoplasm|Bladder Carcinoma|Breast Carcinoma|Cervical Carcinoma|Colon Carcinoma|Colorectal Carcinoma|Endometrial Carcinoma|Esophageal Carcinoma|Gastric Carcinoma|Glioma|Head and Neck Carcinoma|Kidney Carcinoma|Liver and Intrahepatic Bile Duct Carcinoma|Lung Carcinoma|Lymphoma|Malignant Uterine Neoplasm|Melanoma|Ovarian Carcinoma|Pancreatic Carcinoma|Plasma Cell Myeloma|Prostate Carcinoma|Rectal Carcinoma|Recurrent Bladder Carcinoma|Recurrent Breast Carcinoma|Recurrent Cer August 12, 2015 Phase 2
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    References
    Preparing Stock Solutions
    Concentration Volume (DMSO) Mass 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
    Cell Assay
    [1]

    AZD-9291 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1].

    PC-9 cells are seeded into T75 flasks (5×105 cells/flask) in RPMI growth media and incubated at 37°C, 5% CO2. The following day the media is replaced with media supplemented with a concentration of EGFR inhibitor equal to the EC50 concentration predetermined in PC-9 cells. Media changes are carried out every 2-3 days and resistant clones allowed to grow to 80% confluency prior to the cells being trypsinised and reseeded at the original seeding density in media containing twice the concentration of EGFR inhibitor. Dose escalations are continued until a final concentration of 1.5 μM Gefitinib, 1.5 μM Afatinib, 1.5 μM WZ4002 or 160 nM AZD-9291 are achieved[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1][2]

    AZD-9291 is suspended in 1% Polysorbate 80 (Mice)[1].
    AZD-9291 is suspended in 0.5% w/v HPMC/0.1% w/v Tween in deionized water at a concentration of 20 mg/mL (Rat)[2].

    Mice[1]
    The EGFRL858R and EGFRL858R+T790M mice (male and female) are used. AZD-9291 is suspended in 1% Polysorbate 80 and administered via oral gavage once daily at the doses of 7.5 mg/kg and 5 mg/kg, respectively. Mice are imaged weekly at the Vanderbilt University Institute of Imaging Science. For immunoblot analysis, mice are treated for eight hours with drug as described before dissection and flash freezing of the lungs. Lungs are pulverized in liquid nitrogen before lysis.
    Rat[2]
    The male RccHan:WIST rats (10-week-old) are received a single oral dose of AZD-9291 (200 mg/kg). Blood glucose levels are measured using an Accuchek Active meter. Serum insulin concentrations are determined using a commercial rat ELISA kit. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    499.61

    Formula

    C₂₈H₃₃N₇O₂

    CAS No.

    1421373-65-0

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 30 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    Purity: 99.95%

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    Product Name:
    AZD-9291
    Cat. No.:
    HY-15772
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