1. PI3K/Akt/mTOR
    Autophagy
  2. mTOR
    Autophagy

AZD2014 (Synonyms: Vistusertib; AZD-2014)

Cat. No.: HY-15247 Purity: 98.99%
Data Sheet SDS Handling Instructions

AZD2014 is a small-molecule ATP competitive mTOR inhibitor with IC50 of 2.81 nM.

For research use only. We do not sell to patients.
AZD2014 Chemical Structure

AZD2014 Chemical Structure

CAS No. : 1009298-59-2

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10 mg $120 In-stock
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100 mg $400 In-stock
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Top Publications Citing Use of Products

    AZD2014 purchased from MCE. Usage Cited in: Patent. US 20160089377 A1.

    Treatment with WYE125132 rescues cellular, synaptic and molecular abnormalities in Cntnap2 mutants. Bar graphs (top) indicate that the dramatic increase in phosphorylation of S6 (Phospho-S6: S6) in the cortex of Cntnap2−/− and Cntnap2+/− mice is completely reversed with by treatment with WYE125132. In Bar graphs, each pair reflects untreated (left) and treated (right) values. Representative immunoblots are shown (bottom).

    AZD2014 purchased from MCE. Usage Cited in: Patent. US 20160089377 A1.

    Western blot of cortical extracts from Cntnap2 mutant or wild-type mice treated with vehicle or various mTOR pathway inhibitors, showing staining for the presence of phosphorylated S6. Individual mice are tested, and are represented in the lanes as follows. Lane 1=Cntnap2+/− mouse 9-10 weeks old treated with vehicle as for AZD2014; Lane 2=Cntnap2+/− mouse 7.3 months old treated with Rapamycin; Lane 3=Cntnap2+/− mouse 6.3 months old treated with Torin 2; Lane 4=Cn
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    AZD2014 is a small-molecule ATP competitive mTOR inhibitor with IC50 of 2.81 nM.

    IC50 & Target

    IC50: 2.81 nM (mTOR)[1]

    In Vitro

    The inhibitory effects of AZD2014 are measured against isolated recombinant mTOR enzyme (IC50 of 2.81 nM) as well as in cellular assays measuring both mTORC1 and mTORC2 activities. In MDAMB468 cells, AZD2014 decreases the phosphorylation of the mTORC1 substrate ribosomal protein S6 (Ser235/236) with a mean IC50 value of 210 nM and the mTORC2 substrate AKT (Ser473) with a mean IC50 value of 78 nM[1].

    In Vivo

    AZD2014 induces dose-dependent tumor growth inhibition in several xenograft and primary explant models. The antitumor activity of AZD2014 is associated with modulation of both mTORC1 and mTORC2 substrates, consistent with its mechanism of action. The pharmacokinetics of AZD2014 in mice is tested upon administration of doses between 7.5 and 15 mg/kg. A dose-dependent increase in Cmax and AUC is observed following single dose and repeat dosing of AZD2014: Cmax range from 1 to 16 μM and AUC range from 220 to 5,042 μM·h across this dose range. The pharmacodynamic effect of AZD2014 against an mTORC1 biomarker (phosphorylation of S6) and an mTORC2 biomarker (phosphorylation of AKT) is assessed in SCID mice bearing MCF7 xenografts following administration of 3.75, 7.5, and 15 mg/kg AZD2014. There is a good relationship between the drug plasma concentrations and biomarker levels (estimated p-AKT IC50 of 0.119 μM total, 53% SE, and estimated p-S6 IC50 0.392 μM, 28.8% SE)[1].

    Clinical Trial
    NCT Number Sponsor Condition Start Date Phase
    NCT03061708 Samsung Medical Center Stomach Neoplasms February 1, 2017 Phase 2
    NCT02193633 Royal Marsden NHS Foundation Trust|Institute of Cancer Research, United Kingdom|AstraZeneca Advanced Cancer April 2013 Phase 1
    NCT03166904 Samsung Medical Center Solid Tumor July 2017 Phase 2
    NCT02064608 Cambridge University Hospitals NHS Foundation Trust|AstraZeneca Prostate Cancer October 2014 Phase 1
    NCT01597388 AstraZeneca Advanced Metastatic Breast Cancer May 8, 2012 Phase 1
    NCT02619864 Canadian Cancer Trials Group|AstraZeneca Glioblastoma Multiforme November 2015 Phase 1|Phase 2
    NCT02780830 AstraZeneca Core: Relapsed or Refractory Diffuse Large B-Cell Lymphoma|Module 1: Non-GCB Diffuse Large B-Cell Lymphoma June 2016 Phase 1
    NCT01026402 AstraZeneca Advanced Solid Malignancies December 2009 Phase 1
    NCT01793636 Queen Mary University of London|AstraZeneca|Cancer Research UK Metastatic Clear Cell Renal Carcinoma February 2013 Phase 2
    NCT03071874 Massachusetts General Hospital|National Cancer Institute (NCI)|AstraZeneca Meningioma April 15, 2017 Phase 2
    NCT02208375 M.D. Anderson Cancer Center|AstraZeneca|National Cancer Institute (NCI) Breast Cancer|Malignant Female Reproductive System Neoplasm November 2014 Phase 1|Phase 2
    NCT02831257 Massachusetts General Hospital|AstraZeneca|United States Department of Defense Neurofibromatosis 2|Meningioma July 2016 Phase 2
    NCT02583542 Queen Mary University of London|Cancer Research UK|AstraZeneca Triple-Negative Breast Cancer|Squamous Cell Lung Cancer|Non-squamous Cell Lung Cancer With KRAS Mutations|Non-squamous Cell Lung Cancer With Wild-type KRAS June 2015 Phase 1|Phase 2
    NCT02403895 AstraZeneca Squamous Non Small Cell Lung Cancer April 2015 Phase 2
    NCT02398747 AstraZeneca Advanced Solid Malignancies March 17, 2015 Phase 1
    NCT03106155 Samsung Medical Center|AstraZeneca Small Cell Lung Cancer April 2017 Phase 2
    NCT03082833 Samsung Medical Center Cancer of Stomach February 1, 2017 Phase 2
    NCT03166176 Samsung Medical Center Solid Tumor July 2017 Phase 2
    NCT02599714 AstraZeneca|SCRI Development Innovations, LLC Advanced and Metastatic Breast Cancer December 7, 2015 Phase 1|Phase 2
    NCT02640755 AstraZeneca|Quintiles, Inc. Solid Malignancies January 28, 2016 Phase 1
    NCT02216786 Queen Mary University of London|AstraZeneca Estrogen Receptor Positive Breast Cancer January 2014 Phase 2
    NCT02730923 Centre Leon Berard Endometrial Carcinoma|Metastatic Carcinoma|Hormone Receptor Positive Tumor April 2016 Phase 1|Phase 2
    NCT02449655 Samsung Medical Center Advanced Gastric Adenocarcinoma February 12, 2015 Phase 2
    NCT01884285 AstraZeneca Advanced Castrate-resistant Prostate Cancer CRPC|Squamous Non-Small Cell Lung Cancer sqNSCLC|Triple Negative Breast Cancer TNBC July 9, 2013 Phase 1
    NCT02576444 Joseph Paul Eder|Dana-Farber Cancer Institute|Vanderbilt-Ingram Cancer Center|Yale University Cancer November 2015 Phase 2
    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
    NCT02117167 UNICANCER|IFCT|Fondation ARC|AstraZeneca Non-small Cell Lung Cancer Metastatic April 23, 2014 Phase 2
    NCT02299999 UNICANCER|Fondation ARC|AstraZeneca Metastatic Breast Cancer April 7, 2014 Phase 2
    NCT02813135 Gustave Roussy, Cancer Campus, Grand Paris|National Cancer Institute, France Children, Adolescents and Young Adults With Refractory or Recurrent Malignancies June 2016 Phase 1|Phase 2
    NCT02546661 AstraZeneca Muscle Invasive Bladder Cancer October 3, 2016 Phase 1
    View MoreCollapse
    References
    Preparing Stock Solutions
    Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
    1 mM 2.1620 mL 10.8099 mL 21.6198 mL
    5 mM 0.4324 mL 2.1620 mL 4.3240 mL
    10 mM 0.2162 mL 1.0810 mL 2.1620 mL
    Kinase Assay
    [1]

    Recombinant truncated FLAG-tagged mTOR expressed in HEK 293 cells is used in biochemical assays, together with a biotinylated p70S6K peptide substrate. Streptavidin donor and protein A acceptor beads are used to assemble the capture complex for generation of the assay signal. The activity of the lipid kinases, PI3K alpha, beta, delta, and gamma are measured using recombinant proteins and the lipid PIP2 as substrate. Assays for ATM and DNA-PK activity are performed. The mTOR cellular activity is measured in MDAMB468 cells, using an Acumen laser scanning cytometer to analyze the levels of phosphorylation of S6 (Ser235/236) and AKT (Ser473)[1].

    Cell Assay
    [1]

    AZD2014 is prepared in DMSO (10 mM) and stored under nitrogen, and then diluted with appropriate media before use[1].

    Cells are plated in 96-well plates for the indicated time. For CellTiterGlo assays: CellTiterGlo is mixed with the cells. Cells are normalized to day 0 control and net growth is determined using the following formula: ((x−y)/(z−y))=net growth, where x=reading of treated sample at end of study, y=average reading on day 0, and z=reading of DMSO-treated sample at end of study. The concentration of DMSO does not exceed 0.03% for any experiment. For MTS assays: adherent cell lines are grown in 96-well plates. MTS reagent is added on day 0 and on day 3 post-AZD2014 addition. Suspension lines are assayed using the Alamar Blue reagent, 72 hours after AZD2014 addition[1].

    Animal Administration
    [1]

    AZD2014 is dissolved in captisol, and diluted to a final captisol concentration of 30% (w/v) (Mice)[1].

    Mice[1]
    MCF7 experiments: 5×106 MCF7 cells are injected s.c. in a volume of 0.1 mL in male SCID mice and are randomized into control and treatment groups when tumor size reach 0.2 cm3. AZD2014 is dissolved in captisol, and diluted to a final captisol concentration of 30% (w/v). AZD2014 is administered by oral gavage (0.1 mL/10 g body weight). The control group receive vehicle only. Tumor volumes (measured by calliper), animal body weight and condition are recorded twice weekly for the duration of the study. The tumor volume is calculated (taking length to be the longest diameter across and width to be the corresponding perpendicular diameter) using the formula: (length×width)×√(length×width)×(π/6).

    References
    M.Wt

    462.54

    Formula

    C₂₅H₃₀N₆O₃

    CAS No.

    1009298-59-2

    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

    10 mM in DMSO

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

    Purity: 98.99%

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    Product Name:
    AZD2014
    Cat. No.:
    HY-15247
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