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

AZD 6482 (Synonyms: KIN-193)

Cat. No.: HY-10344 Purity: 99.26%
Handling Instructions

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

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10 mM * 1 mL in DMSO USD 81 In-stock
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Customer Review

Based on 20 publication(s) in Google Scholar

Other Forms of AZD 6482:

Top Publications Citing Use of Products

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

    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).

    AZD 6482 purchased from MCE. Usage Cited in: Nat Commun. 2015 Oct 7;6:8501.

    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 MCE. Usage Cited in: Oncogene. 2016 Jul 7;35(27):3607-12.

    (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 MCE. Usage Cited in: Cell Discov. 2016 Sep 20;2:16030.

    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 MCE. Usage Cited in: Tumour Biol. 2016 Nov;37(11):14831-14839.

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

    AZD 6482 purchased from MCE. Usage Cited in: Cancer Lett. 2019 Jan;440-441:54-63.

    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 MCE. Usage Cited in: Oncol Rep. 2019 Jan;41(1):125-132.

    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.
    • 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].

    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].

    Clinical Trial
    Molecular Weight

    408.45

    Formula

    C₂₂H₂₄N₄O₄

    CAS No.

    1173900-33-8

    SMILES

    O=C1N2C(C([[email protected]](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 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 100 mg/mL (244.83 mM)

    *"≥" means soluble, but saturation unknown.

    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
    10 mM 0.2448 mL 1.2241 mL 2.4483 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 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

    • 2.

      Add each solvent one by one:  10% DMSO    90% corn oil

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

    *All of the co-solvents are provided by MCE.
    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

    Purity: 99.26%

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    Keywords:

    AZD 6482KIN-193AZD6482AZD-6482KIN193KIN 193PI3KAutophagyPhosphoinositide 3-kinaseInhibitorinhibitorinhibit

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