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

ZSTK474 

Cat. No.: HY-50847 Purity: 99.56%
Data Sheet SDS Handling Instructions

ZSTK474 is an ATP-competitive pan-class I PI3K inhibitor with IC50s of16 nM, 44 nM, 4.6 nM and 49 nM for PΙ3Κα, PI3Kβ, PI3Kδ and PI3Kγ, respectively.

For research use only. We do not sell to patients.
ZSTK474 Chemical Structure

ZSTK474 Chemical Structure

CAS No. : 475110-96-4

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $55 In-stock
10 mg $50 In-stock
50 mg $70 In-stock
100 mg $95 In-stock
200 mg $140 In-stock
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    ZSTK474 purchased from MCE. Usage Cited in: Clin Cancer Res. 2014 Nov 1;20(21):5483-95.

    Effects of GSK1904529A and AZD6244 as single agents, respectively, on mediators of IGF-1R- and ERK1/ERK2-signaling pathways.(A–B) Effect of GSK1904529A on phosphorylation of IGF-1R (A) and Erk1/Erk2 (B). (C–E) Effect of AZD6244 on phosphorylation of IGF-1R (C), IGF-1R protein expression levels (D), and phosphorylation of Erk1/Erk2 (E). GSK1904529A is observed to inhibit phosphorylation of IGF-1R in a concentration-dependent manner (A), however shows no inhibitory activity against phosphorylation
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    ZSTK474 is an ATP-competitive pan-class I PI3K inhibitor with IC50s of16 nM, 44 nM, 4.6 nM and 49 nM for PΙ3Κα, PI3Kβ, PI3Kδ and PI3Kγ, respectively.

    IC50 & Target

    IC50: 16 nM (PΙ3Κα), 44 nM (PI3Kβ), 4.6 nM (PI3Kδ), 49 nM (PI3Kγ)[1]

    In Vitro

    Lineweaver-Burk plot analysis revealed that ZSTK474 inhibits all four PI3K isoforms in an ATP-competitive manner. The Ki values determined for the four PI3K isoforms showed that ZSTK474 inhibited the PI3Kδ isoform most effectively with a Ki of 1.8 nM, whereas the other isoforms are inhibited with 4-10-fold higher Ki values. Therefore, ZSTK474 should be regarded as a pan-PI3K inhibitor. We also determined the IC50 values for inhibiting the four PI3K isoforms with ZSTK474 and LY294002. The IC50 values of ZSTK474 (16, 44, 4.6 and 49 nM for PI3Kα, PI3Kβ, PI3Kδ and PI3Kγ, respectively) are shown to be consistent with the Ki values (6.7, 10.4, 1.8 and 11.7 nM for PI3Kα, PI3Kβ, PI3Kδ and PI3Kγ, respectively), which further supported the idea that ZSTK474 inhibits PI3Kδ most potently. Even at a concentration of 100 µM, ZSTK474 inhibits mTOR activity rather weakly[1].

    In Vivo

    In mice subjected to MCAO, treatment with ZSTK474 is tested at dosages of 50, 100, 200, and 300 mg/kg. Since the 200 mg/kg dose produces significant improvement and no obvious toxic effects (P<0.01), mice are treated with ZSTK474 at a dose of 200 mg/kg/day daily for three post-MCAO days during the remaining experiments of this study. Neurological function is examined in mice suffered from MCAO followed by 24, 48, and 72 h of reperfusion. In the ZSTK474 group, neurological function scores are significantly better than the control group except the corner test[2].

    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.3957 mL 11.9786 mL 23.9573 mL
    5 mM 0.4791 mL 2.3957 mL 4.7915 mL
    10 mM 0.2396 mL 1.1979 mL 2.3957 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [1]

    The linear phase of each kinetic reaction is defined at the respective enzyme amount (0.05, 0.1, 0.12 and 1 µg/mL for PI3Kα, PI3β, PI3δ and PI3γ, respectively) and reaction time (20 min). PI3K activity is assayed at various concentrations of ATP (5, 10, 25, 50, 100 µM) in the presence of increasing concentrations of ZSTK474. A Lineweaver-Burk plot is developed by plotting 1/v (the inverse of v, where v is obtained by subtracting the HTRF signal of the kinase test sample from the HTRF signal of the minus-enzyme control) versus 1/[ATP] (the inverse of the ATP concentration). For the minus-enzyme control, PIP2 is incubated with ATP in the absence of kinase. To determine the Ki value (inhibition constant) of ZSTK474 for each PI3K isoform, the slope of the respective Lineweaver-Burk plot is replotted against the ZSTK474 concentration. The Ki values are calculated by analysis using GraphPad Prism 4[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    ZSTK474 is suspended in 5 % hydroxypropylcellulose in water as a solid dispersion (Mice)[2].

    Mice[2]
    Mice are randomly assigned to receive different doses of ZSTK474 (50, 100, 200, and 300 mg/kg) to determine the optimum dose; in our experiment, the optimum dose is 200 mg/kg. Then mice are randomly assigned to one of three groups: a sham-operated group (phosphate-buffered saline, PBS); a control group (MCAO+PBS); a ZSTK474-treated group (MCAO+ZSTK474). In the ZSTK474-treated group, the mice are given the optimum dose of 200 mg/kg ZSTK474. In the sham-operated group and control group, mice are given an equivalent volume of PBS. All mice receive that same dose daily via oral gavage beginning at 6 h after the onset of focal ischemia and continuing for two more days, i.e., for a total of 3 days.
    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    417.41

    Formula

    C₁₉H₂₁F₂N₇O₂

    CAS No.

    475110-96-4

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    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.

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    Cat. No.:
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