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 an irreversible and mutant selective EGFR inhibitor with IC50s of 12 and 1 nM against EGFRL858R and EGFRL858R/T790M, respectively.

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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10 mM * 1 mL in DMSO $55 In-stock
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10 mg $70 In-stock
50 mg $120 In-stock
100 mg $150 In-stock
200 mg $210 In-stock
500 mg $330 In-stock
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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 an irreversible and mutant selective EGFR inhibitor with IC50s of 12 and 1 nM against EGFRL858R and EGFRL858R/T790M, respectively.

    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
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    References
    Preparing Stock Solutions
    Concentration Volume 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
    Please refer to the solubility information to select the appropriate solvent.
    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

    Please store the product under the recommended conditions in the Certificate of Analysis.

    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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    Inquiry Information

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