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

Dactolisib  (Synonyms: BEZ235; NVP-BEZ235)

Cat. No.: HY-50673 Purity: 99.94%
COA Handling Instructions

Dactolisib (BEZ235) is an orally active and dual pan-class I PI3K and mTOR kinase inhibitor with IC50s of 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR, respectively. Dactolisib (BEZ235) inhibits both mTORC1 and mTORC2.

For research use only. We do not sell to patients.

Dactolisib Chemical Structure

Dactolisib Chemical Structure

CAS No. : 915019-65-7

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Customer Review

Based on 55 publication(s) in Google Scholar

Other Forms of Dactolisib:

Top Publications Citing Use of Products

50 Publications Citing Use of MCE Dactolisib

WB

    Dactolisib purchased from MedChemExpress. Usage Cited in: J Exp Clin Cancer Res. 2018 Aug 9;37(1):188.  [Abstract]

    Representative images of the western blotting analysis of TSSC3, ATG5, P62, LC3, Src, Akt, mTOR and their phosphorylated versions in MTF and SaOS2 cells. Cells are treated with TSSC3-overexpression, IGF-1, p-YEEI, and BEZ235 separately or in combination.

    Dactolisib purchased from MedChemExpress. Usage Cited in: Biomed Res Int. 2018 Aug 5;2018:8372085.  [Abstract]

    Changes of p-AKT and p-p70 S6K proteins after treatment with NVP-BEZ235 in Ishikawa and Ishikawa-TAX cells. Changes of p-AKT and p-p70 S6K proteins after treatment of Ishikawa and Ishikawa-TAX cells with NVP-BEZ235.

    Dactolisib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2017 Jun 8;8:15617.  [Abstract]

    Immunoblot analysis of KRAS protein levels in parental (P) and resistant derivatives (R1 and R2) following 4 h treatment with the corresponding inhibitors Rapamycin, AZD2014, MLN0128, BEZ235 and 4EGI-1. Images are cropped for clarity from the same exposure of the same membrane.

    Dactolisib purchased from MedChemExpress. Usage Cited in: Oncotarget. 2017 Jul 11;8(28):45470-45483.  [Abstract]

    Activity of PI3K/AKT/mTOR is monitored by examining phosphorylation of AKT-S473, AKT-T308, and S6 by western blotting.

    Dactolisib purchased from MedChemExpress. Usage Cited in: Leukemia. 2014 Sep;28(9):1819-27.  [Abstract]

    Western blot analysis of human T-ALL cell lines treated for 24 hours using DMSO (vehicle control), 1 μM JQ1, 500 nM BEZ235, or both drugs in combination, using the indicated antibodies. Western blot analysis of these T-ALL cell lines following treatment with JQ1, BEZ235 or both drugs in combination reveals cooperative upregulation of BIM protein expression coupled to induction of apoptosis, as assessed by PARP cleavage.
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Dactolisib (BEZ235) is an orally active and dual pan-class I PI3K and mTOR kinase inhibitor with IC50s of 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR, respectively. Dactolisib (BEZ235) inhibits both mTORC1 and mTORC2.

    IC50 & Target[1]

    p110α

    4 nM (IC50)

    p110α-H1047R

    4.6 nM (IC50)

    p110α-E545K

    5.7 nM (IC50)

    p110γ

    5 nM (IC50)

    p110δ

    7 nM (IC50)

    p110β

    75 nM (IC50)

    mTOR

    20.7 nM (IC50)

    mTORC1

     

    mTORC2

     

    Autophagy

     

    In Vitro

    Dactolisib (BEZ235) potently inhibits PI3K in an ATP Competitive Manner. Dactolisib (BEZ235) (250 nM) significantly reduced the phosphorylation levels of the mTOR activated kinase p70S6K. Dactolisib (BEZ235) also leads to a reduction of S235/S236P-RPS6 levels with an IC50 of 6.5 nM, suggesting that Dactolisib (BEZ235) can directly inhibit the mTOR kinase, as the kinase domain of mTOR is highly homologous to the one of class IA PI3K. The activity of Dactolisib (BEZ235) against mTOR is confirmed using a biochemical mTOR K-LISA assay (IC50, 20.7 nM)[1].
    The IC50s of Dactolisib (BEZ235) for HCT116, DLD-1, and SW480 cell lines are 14.3±6.4, 9.0±1.5, and 12.0±1.6 nM, respectively[2].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    In Vivo

    Dactolisib (BEZ235) (45 mg/kg, p.o.) treatment induces colonic tumor regression in a GEM model for sporadic PIK3CA wild-type CRC[2]. Dactolisib (BEZ235) (45 mg/kg) is administered to MENX rats (n=2 each group) by oral gavage and animals are sacrificed 1 or 6 hours after treatment. Immunostains for P-AKT and P-S6 show considerable reduction of the two proteins, and particularly of P-S6, 6 hours after administration of Dactolisib (BEZ235) when compares with PEG-treated rats. At 6 hours after treatment, the pituitary adenomas of Dactolisib (BEZ235)-treated rats has a proteomic profile significantly different from the tumors of placebo-treated rats[3].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Clinical Trial
    Molecular Weight

    469.54

    Formula

    C30H23N5O

    CAS No.
    Appearance

    Solid

    Color

    White to light yellow

    SMILES

    CN(C1=C2C3=CC(C4=CC5=CC=CC=C5N=C4)=CC=C3N=C1)C(N2C6=CC=C(C=C6)C(C)(C#N)C)=O

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    5% TFA : 8.33 mg/mL (17.74 mM; ultrasonic and warming and heat to 60°C)

    DMSO : 7.81 mg/mL (16.63 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    DMF : 2 mg/mL (4.26 mM; Need ultrasonic)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.1297 mL 10.6487 mL 21.2974 mL
    5 mM 0.4259 mL 2.1297 mL 4.2595 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass
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    Volume
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    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

    =
    Concentration (final)

    C2

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    Volume (final)

    V2

    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 0.52 mg/mL (1.11 mM); Clear solution

      This protocol yields a clear solution of ≥ 0.52 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (5.2 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% Corn Oil

      Solubility: ≥ 0.52 mg/mL (1.11 mM); Clear solution

      This protocol yields a clear solution of ≥ 0.52 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (5.2 mg/mL) to 900 μL Corn oil, and mix evenly.

    For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  50% PEG300    50% Saline

      Solubility: 12.5 mg/mL (26.62 mM); Suspended solution; Need ultrasonic

    • Protocol 2

      Add each solvent one by one:  10% 1-Methyl-2-pyrrolidinone    90% PEG300

      Solubility: ≥ 1.1 mg/mL (2.34 mM); Clear solution

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.94%

    References
    Cell Assay
    [2]

    HCT116 (PIK3CA mutant; kinase domain at H1047R), DLD-1 (PIK3CA mutant; helical domain at E545K), and SW480 (PIK3CA wild-type) human CRC cell lines (ATCC) and isogenic DLD-1 PIK3CA mutant and wild-type cells are maintained in DMEM. Cells are plated at different initial densities (HCT116: 3,000 cells/well, DLD-1: 5,500 cells/well, SW480: 4,500 cells/well, DLD-1 PIK3CA mutant: 7,000 cells/well, and DLD-1 PIK3CA wild-type: 9,000 cells/well) to account for differential growth kinetics. After 16 hours, cells are incubated with increasing concentrations of BEZ235 (10, 100, 1000 nM), and drug-containing growth medium is changed every 24 hours. Cell viability is assessed 16 hours after the initial plating and 48 hours after initiation of drug treatment using the colorimetric MTS assay CellTiter 96 AQueous One Solution Cell Proliferation Assay. Cell viability after drug treatment is normalized to that of untreated cells also grown for 48 hours. IC50 values are calculated using 4 parameter nonlinear regression in GraphPad Prism 5[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2][3]

    Mice[2]
    Tumor-bearing Apc CKO mice are randomly assigned to treatment with either control vehicle alone (n=8) or 45 mg/kg body weight BEZ235 in 10% 1-methyl-2-pyrrolidone/90% PEG 300 (n=8) by daily oral gavage for 28 days. The treatment dose is chosen based on literature indicating that 40-50 mg/kg body weight BEZ235 effectively treats murine tumor models without adverse effects. Base on pharmacokinetic studies demonstrating maximal tissue concentration one hour after NVP-BEZ235 administration, tumor-bearing mice are sacrificed one hour after final treatment dose. Colonic tumor volume is assessed using calipers (width×length×height) and tumors are harvested for both western blot analysis and immunohistochemistry.
    Rats[3]
    MENX-affected rats used. Three doses of BEZ235 are tested in MENX rats: 20, 30, and 45 mg/kg. As the two higher doses causes a weight loss >10% after 10 days of treatment, the dose of 20 mg/kg is used for further studies. For MRI studies, MENX-affected rats at 7 to 8 months of age (with sizeable adenomas but still in good general health) are treated for 14 days with BEZ235 (20 mg/kg) or placebo (PEG) administered daily per oral gavage.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMF / DMSO / 5% TFA 1 mM 2.1297 mL 10.6487 mL 21.2974 mL 53.2436 mL
    DMSO / 5% TFA 5 mM 0.4259 mL 2.1297 mL 4.2595 mL 10.6487 mL
    10 mM 0.2130 mL 1.0649 mL 2.1297 mL 5.3244 mL
    15 mM 0.1420 mL 0.7099 mL 1.4198 mL 3.5496 mL
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    Dactolisib Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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