1. PI3K/Akt/mTOR Autophagy
  2. PI3K Autophagy
  3. AZD 6482

AZD 6482 (KIN-193) is a potent and selective p110β inhibitor with an IC50 of 0.69 nM.

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

AZD 6482 Chemical Structure

AZD 6482 Chemical Structure

CAS No. : 1173900-33-8

Size Price Stock Quantity
Free Sample (0.1 - 0.5 mg)   Apply Now  
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
USD 81 In-stock
Solution
10 mM * 1 mL in DMSO USD 81 In-stock
Solid
5 mg USD 90 In-stock
10 mg USD 150 In-stock
25 mg USD 250 In-stock
50 mg USD 450 In-stock
100 mg   Get quote  
200 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 27 publication(s) in Google Scholar

Other Forms of AZD 6482:

Top Publications Citing Use of Products

    AZD 6482 purchased from MedChemExpress. Usage Cited in: Cancer Lett. 2019 Jan;440-441:54-63.  [Abstract]

    The cells are transfected with either the negative control (siNC) or BTF3 siRNA for 12 hours followed by BKM-120 or AZD-6482 treatment for 48 hours. The protein abundance is determined by an immunoblotting analysis.

    AZD 6482 purchased from MedChemExpress. Usage Cited in: Oncol Rep. 2019 Jan;41(1):125-132.  [Abstract]

    The expression levels of Bcl-2, Bax and related proteins of the PI3K signalling pathway are used to assess the inhibitory effect of AZD6482. Each protein is analysed in triplicate, and a representative experiment is shown.

    AZD 6482 purchased from MedChemExpress. Usage Cited in: Cell Discov. 2016 Sep 20;2:16030.  [Abstract]

    Effects of combined inhibition of PI3K and STAT3 pathways on PTEN-mutated T-ALL cells. (a) Short-term treatment of Ba/F3-shPTEN-NTRK2-Tel cells with isoform-selective inhibitors and Pan-PI3K inhibitor GDC-0032. Cells are treated with DMSO, BYL719, KIN193, GS-1101, GDC-0032 (1 μM) or JAK–STAT inhibitor AZD-1480 (1 μM) for 3 h (n=3) for each treatment. (b) Immunoblot analysis of P-Akt and p-S6 in PF382 and JURKAT cells. Cells are treated with the same inhibitors as in a. (c) Combination of siNTRK2

    AZD 6482 purchased from MedChemExpress. Usage Cited in: Oncogene. 2016 Jul 7;35(27):3607-12.  [Abstract]

    (A) Immunoblot analyses in HCC1569 cells treated with BYL719, KIN193 (MedChemexpress) or BKM120 (μM). (B, C) Immunoblot analyses in BT474 and BT474-shPTEN cells treated as indicated in (A).

    AZD 6482 purchased from MedChemExpress. Usage Cited in: Tumour Biol. 2016 Nov;37(11):14831-14839.  [Abstract]

    Western blot analysis of PI3K signaling in NIC-PTENL/L cells treated with BYL719, AZD6482, or BKM120.

    AZD 6482 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2015 Oct 7;6:8501.  [Abstract]

    Western blot analysis of Akt signalling in whole BM cells at 7 DPI. Freshly isolated BM cells are treated with DMSO, BYL719, KIN193, GS1101 or NVSPI35 at the 1-μM dose for 2 h (n=6) for each treatment.

    AZD 6482 purchased from MedChemExpress. Usage Cited in: Cancer Discov. 2012 May;2(5):425-33.  [Abstract]

    Effects of KIN-193, GDC-0941, PIK-75 and IC87114 on AKT phosphorylation in PTEN-deficient cell lines as indicated. Representative western blots are shown. Bar graphs represent mean ± SD of western blot quantitations of AKTT308 (n=3).
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    AZD 6482 (KIN-193) is a potent and selective p110β inhibitor with an IC50 of 0.69 nM.

    IC50 & Target[1]

    PI3Kβ

    0.69 nM (IC50)

    PI3Kδ

    13.6 nM (IC50)

    PI3Kγ

    47.8 nM (IC50)

    PI3Kα

    136 nM (IC50)

    PI3K-C2β

    54.1 nM (IC50)

    hVps34

    3390 nM (IC50)

    DNA-PK

    53.7 nM (IC50)

    mTOR

    3930 nM (IC50)

    PI4Kα

    8830 nM (IC50)

    Autophagy

     

    In Vitro

    An in vitrokinase assay demonstrates that AZD 6482 (KIN-193) is highly potent in the inhibition of p110β’s kinase activity (IC50 of 0.69 nM) and has 200, 20, and 70-fold selectivity over p110α, p110δ, and p110γ isoforms, respectively. AZD 6482 also exhibits selectivity of ~80 fold over PI3K-C2β and DNA-PK and more than 1,000-fold over other phosphatidylinositol-3 kinase–related kinases (PIKKs). An inhibitor-kinase interaction profiling of AZD 6482 against a panel of 433 kinases using the KinomeScan approach demonstrates that AZD 6482 is highly selective in its interaction with PI3Ks. To determine whether AZD 6482 selectively targets PTEN-deficient tumors, the effect of AZD 6482 is tested on cell proliferation on a large panel of 422 cancer cell lines using high-throughput tumor cell line profiling. 35% of cell lines with PTEN mutations (20 out of 57) and 16% of cell lines with wild-type PTEN (58 out of 365) are sensitive to AZD 6482 with a threshold of EC50<5 µM[1].

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

    In Vivo

    To determine the pharmacodynamics of AZD 6482 (KIN-193) in tumors in vivo, rat fibroblast (Rat1) cells are engineered to express both p53DD, a dominant negative mutant of p53, and a constitutively activated myr-p110β (Rat1-CA-p110β) to enable these cells to form xenograft tumors in mice. For comparison, an isogenic Rat1 cell line expressing p53DD and myr-p110α (Rat1-CA-p110α) is also generated. Rat1-CA-p110α and Rat1-CA-p110β cells are introduced subcutaneously into the contralateral flanks of athymic mice such that tumors driven by activated p110α or p110β would be exposed to identical conditions and that concern about animal-to-animal variability could be eliminated. When tumors reach a volume of ~500 mm3, the tumor-bearing mice receives a single IP injection of AZD 6482 (10 mg/kg). The plasma concentration of AZD 6482 is highest at 1 hour post-injection and declined to undetectable levels by 4h. Concentrations of AZD 6482 in both the CA-p110α- and CA-p110β-driven tumors parallel the plasma concentrations. Analyses of tumor lysates harvested at various time points after AZD 6482 injection reveal that the phosphorylation of AKT is significantly reduced at 1hour after AZD 6482 injection in Rat1-CA-p110β tumors, but remain unchanged in Rat1-CAp110α tumors[1].

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

    Clinical Trial
    Molecular Weight

    408.45

    Formula

    C22H24N4O4

    CAS No.
    Appearance

    Solid

    Color

    White to light yellow

    SMILES

    O=C1N2C(C([C@H](NC3=CC=CC=C3C(O)=O)C)=CC(C)=C2)=NC(N4CCOCC4)=C1

    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: 

    DMSO : 50 mg/mL (122.41 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.4483 mL 12.2414 mL 24.4828 mL
    5 mM 0.4897 mL 2.4483 mL 4.8966 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
    =
    Concentration
    ×
    Volume
    ×
    Molecular Weight *

    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

    ×
    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: ≥ 2.5 mg/mL (6.12 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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: ≥ 2.5 mg/mL (6.12 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 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 (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

    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: 99.56%

    References
    Kinase Assay
    [1]

    AZD 6482 (KIN-193) is profiled at a concentration of 10 µM against a diverse panel of 433 kinases. Scores for primary screen hits are reported as percent of the DMSO control (% control). For kinases where no score is shown, no measurable binding is detected. The lower the score, the lower the Kd is likely to be, such that scores of zero represent strong hits. Scores are related to the probability of a hit, but are not strictly an affinity measurement. At a screening concentration of 10 µM, a score of less than 10% implies that the false positive probability is less than 20% and the Kd is most likely less than 1 µM. A score between 1-10% implies that the false positive probability is less than 10%, although it is difficult to assign a quantitative affinity from a single-point primary screen. A score of less than 1% implies that the false positive probability is less than 5% and the Kd is most likely less than 1 µM[1].

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

    Cell Assay
    [1]

    Cell viability is determined. Briefly, cells are seeded in medium containing 5% FBS at a density insuring cell growth throughout drug treatment (~15% for most cell lines). Drug treatment is started 24 h post seeding and continued for 72 h. Cell are fixed and stained using Syto60, a red fluorescent DNA stain. The relative cell number is calculated by taking the ratio of the relative fluorescence intensity from drug treated wells over untreated wells after background subtraction (cells-free wells). Nine doses of AZD 6482 (KIN-193) are used in 2-fold dilution steps ranging from 5.12 µM to 0.02 µM. IC50, corresponding to 50% cell number compared to control (untreated) wells, is determined using a fixed top and bottom sigmoidal fitting algorithm implemented in PipelinePilot[1].

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

    Animal Administration
    [1]

    Mice[1]
    Approximately 6-8 week-old female nude mice are injected s.c. with Rat1-Myr-HA-p110α(Rat1-CAp110α) cells (1×106 cells in 40% matrigel) in one flank (site 1) and Rat1-Myr-HA-p110β (Rat1-CAp110β) cells (0.5×106 cells in 10% matrigel) in the contralateral flank (site 2). When tumors grow to ~500 mm3, mice are dosed once by ip injection with AZD 6482 formulated in 7.5% NMP, 40% PEG400, 52.5% dH2O at 0.1 mL/10g body weight and 10 mg/kg. Tumors are collected at 0, 1, 4, 8, and 24 h following compound administration and blood samples are obtained by direct heart puncture. Serum is separated and stored at -80°C. The drug concentrations in serum and tumor samples are assessed by LC-MS/MS analysis by the DMPK group.

    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
    DMSO 1 mM 2.4483 mL 12.2414 mL 24.4828 mL 61.2070 mL
    5 mM 0.4897 mL 2.4483 mL 4.8966 mL 12.2414 mL
    10 mM 0.2448 mL 1.2241 mL 2.4483 mL 6.1207 mL
    15 mM 0.1632 mL 0.8161 mL 1.6322 mL 4.0805 mL
    20 mM 0.1224 mL 0.6121 mL 1.2241 mL 3.0604 mL
    25 mM 0.0979 mL 0.4897 mL 0.9793 mL 2.4483 mL
    30 mM 0.0816 mL 0.4080 mL 0.8161 mL 2.0402 mL
    40 mM 0.0612 mL 0.3060 mL 0.6121 mL 1.5302 mL
    50 mM 0.0490 mL 0.2448 mL 0.4897 mL 1.2241 mL
    60 mM 0.0408 mL 0.2040 mL 0.4080 mL 1.0201 mL
    80 mM 0.0306 mL 0.1530 mL 0.3060 mL 0.7651 mL
    100 mM 0.0245 mL 0.1224 mL 0.2448 mL 0.6121 mL
    • No file chosen (Maximum size is: 1024 Kb)
    • If you have published this work, please enter the PubMed ID.
    • Your name will appear on the site.

    AZD 6482 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.

    Your Recently Viewed Products:

    Inquiry Online

    Your information is safe with us. * Required Fields.

    Product Name

     

    Salutation

    Applicant Name *

     

    Email Address *

    Phone Number *

     

    Organization Name *

    Department *

     

    Requested quantity *

    Country or Region *

         

    Remarks

    Bulk Inquiry

    Inquiry Information

    Product Name:
    AZD 6482
    Cat. No.:
    HY-10344
    Quantity:
    MCE Japan Authorized Agent: