1. Cell Cycle/DNA Damage
  2. Checkpoint Kinase (Chk)

AZD-7762 

Cat. No.: HY-10992 Purity: 98.68%
Data Sheet SDS Handling Instructions

AZD-7762 is a potent ATP-competitive checkpoint kinase (Chk) inhibitor in with IC50 of 5 nM for Chk1.

For research use only. We do not sell to patients.
AZD-7762 Chemical Structure

AZD-7762 Chemical Structure

CAS No. : 860352-01-8

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $77 In-stock
5 mg $70 In-stock
10 mg $110 In-stock
50 mg $330 In-stock
100 mg $468 In-stock
200 mg   Get quote  
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    AZD-7762 purchased from MCE. Usage Cited in: PLoS One. 2017 Jan 18;12(1):e0170308.

    Inhibition of nuclear actin filament formation by Chek1/2 inhibitor, AZD7762 (AZD). No nuclear actin filament formation is observed upon treatment of CEOs with AZD alone.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    AZD-7762 is a potent ATP-competitive checkpoint kinase (Chk) inhibitor in with IC50 of 5 nM for Chk1.

    IC50 & Target

    IC50: 5 nM (ChK1)[1]

    In Vitro

    AZD-7762 (AZD7762) is an equally potent inhibitor of Chk1 and Chk2 in vitro. AZD-7762 potently inhibits Chk1 and Chk2, abrogates DNA damage-induced S and G2 checkpoints, enhances the efficacy of gemcitabine and topotecan, and modulates downstream checkpoint pathway proteins. AZD-7762 potently inhibits Chk1 phosphorylation of a cdc25C peptide with an IC50 of 5 nM as measured by a scintillation proximity assay. The Ki for AZD-7762 is determined to be 3.6 nM. Kinetic characterization suggests that AZD-7762 binds in the ATP-binding site of Chk1 and is thought to compete directly for ATP binding in a reversible manner. AZD-7762 is shown to abrogate the G2 arrest induced by Camptothecin with an average EC50 of 10 nM (n=12) and maximal abrogation in the range of 100 nM[1].

    In Vivo

    In the rat H460-DNp53 xenograft study, AZD-7762 (AZD7762) potentiates the antitumor activity of Gemcitabine in a dose-dependent manner by a decrease in %T/C with increasing dose (48% and 32%, 10 and 20 mg/kg AZD-7762, respectively). In the mouse xenograft study in combination with Irinotecan, SW620 established tumors are treated with vehicle, Irinotecan alone, AZD-7762 alone, or AZD-7762 in combination with Irinotecan. AZD-7762 dosed alone shows insignificant antitumor activity, whereas Irinotecan alone displays striking and significant activity (%T/C with increasing dose is 9 and 1, respectively ). In combination with AZD-7762, %T/C increases significantly to -66% and -67%, respectively[1]. AZD7762 combination with CX-5461 induces cancer cell death of Tp53-null (Tp53-/-) Eμ-Myc lymphoma cells in vitro and in vivo[2].

    Clinical Trial
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    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.7592 mL 13.7961 mL 27.5923 mL
    5 mM 0.5518 mL 2.7592 mL 5.5185 mL
    10 mM 0.2759 mL 1.3796 mL 2.7592 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [1]

    For kinetic analysis, a filter binding assay is used. The assay reaction contains with the following concentrations of ATP [0-600 μM (cold+Ci [33P]ATP), determined Km], Chk1 (0.5 nM), and AZD-7762 (0, 1.5, 5, 10 nM). The reaction is incubated at room temperature for 20 min, stopped by the addition of EDTA, transferred to Streptavidin Flashplate, incubated at room temperature for 1 h, aspirated out, and wells washed with PBS. Plates are counted using a TopCount reader and data are analyzed using proprietary software[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    AZD-7762 (AZD7762) is dissolved in DMSO and stored, and then diluted with appropriate media (DMSO 0.1%) before use[1].

    SW620 (5.5×103 per well) or MDA-MB-231 (5×103 per well) cells are seeded in 96-well plates and incubated overnight. Cells are dosed for 24 h with a 9-point titration of Gemcitabine ranging from 0.01 to 100 nM with or without a constant dose of AZD-7762 (300 nM). Control wells are dosed with vehicle alone (0.1% DMSO) or 300 nM AZD-7762. After 24 h, medium is removed and AZD-7762 alone is added back to the wells treated previously with AZD-7762 for an additional 24 h. Cells are then incubated in drug-free medium for an additional 72 h. The effect on cell proliferation is determined by MTS assay[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1][2]

    AZD-7762 (AZD7762) is formulated in 11.3% hydroxyproplyl-β-cyclodextrin (Mice and Rat)[1].
    AZD7762 (Medchem Express) is prepared in 10.3% -hydroxypropyl-β-cyclodextrin in 0.9% saline (Mice)[2].

    Mice and Rat[1]
    Male NCr mice and male rnu rats are used. For xenograft models in mice, tumor cells are harvested, pelleted by centrifugation for 5 min, and resuspended in sterile PBS. Cells (3×103-6×106) are implanted s.c. into the right flank of the mice in a volume of 0.1 to 0.2 mL using a 25-gauge needle. Tumors are allowed to grow to the designated size of 100 to 200 mm3 before the administration of compound. For xenograft models in rats, Cells are harvested, pelleted by centrifugation for 5 min, and resuspended in 50% sterile PBS and 50% Matrigel. Rats receive a 5 Gy whole-body radiation dose 5 days before cell implantation to improve tumor growth. H460-DNp53 cells (1×107) are implanted s.c., under anesthesia with isoflurane, into the right flank of the rats in a volume of 0.2 mL using a 25-gauge needle. Tumors are allowed to grow to the designated size of 100 to 200 mm3 before the administration of AZD-7762. AZD-7762 (10 and 20 mg/kg) is administered by i.v. injection via the tail vein. Cyclic schedules are used and treatment ranged from three to five cycles. Each cycle includes administration of a standard agent (Gemcitabine or Irinotecan) every 3 days follow by delivery of AZD-7762. Tumor volumes are measured with electronic calipers and calculated.
    Mice [2]
    C57Bl/6 mice are intravenously injected with 2 × 105 Eμ-Myc B-lymphoma cells in PBS and treated with pharmacological inhibitors from 8 days post-injection. Treatment of mice is continued until an ethical end-point is reached; hunched posture, ruffled fur, enlarged lymph nodes, laboured breathing, weight loss greater than 20% of start body weight and limited mobility or paralysis. AZD7762 is delivered intraperitoneally in 10.3% -hydroxypropyl-β-cyclodextrin in 0.9% saline at 20 mg/kg daily on weekdays. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    362.42

    Formula

    C₁₇H₁₉FN₄O₂S

    CAS No.

    860352-01-8

    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

    AZD-7762 is prepared in 10.3% -hydroxypropyl-β-cyclodextrin in 0.9% saline[2].

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

    References

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    AZD-7762
    Cat. No.:
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