1. PI3K/Akt/mTOR
    Stem Cell/Wnt
  2. GSK-3

AZD2858 

Cat. No.: HY-15761 Purity: 99.24%
Handling Instructions

AZD2858 is a potent, orally active GSK-3 inhibitor, with IC50s of 0.9 and 5 nM for GSK-3α and GSK-3β, respectively, used in the research of fracture healing.

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

AZD2858 Chemical Structure

AZD2858 Chemical Structure

CAS No. : 486424-20-8

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 158 In-stock
Estimated Time of Arrival: December 31
10 mg USD 144 In-stock
Estimated Time of Arrival: December 31
50 mg USD 540 In-stock
Estimated Time of Arrival: December 31
100 mg   Get quote  
200 mg   Get quote  

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Top Publications Citing Use of Products

    AZD2858 purchased from MCE. Usage Cited in: J Biol Chem. 2016 Dec 2;291(49):25529-25541.

    Treatment of cells with AZD2858 leads to the induction of both PRC and c-MYC under conditions where the NRF-2α control is unaffected. Human log phase U2OS cells are plated and treated with either vehicle, the GSK-3 inhibitor, AZD2858, or with CCCP for 24 h. Total cell extracts are subjected to immunoblotting using rabbit anti-PRC(1047-1379), mouse anti-c-MYC, rabbit anti-pGSK-3α/β(Ser9/21), rabbit anti-GSK-3α/β or rabbit anti-NRF-2α as the control.

    AZD2858 purchased from MCE. Usage Cited in: J Cell Physiol. 2019 Jan 26.

    Western blot analysis was used to confirm the total protein expression of β-catenin and AR in the LNCaP, DRCaP, BRCaP, and ERCaP cells treated with the wnt/β-catenin activator (AZD2858, 5 nM, 48 hr) or the wnt/β-catenin inhibitor (PNU74654, 129.8 μM, 48 hr).

    AZD2858 purchased from MCE. Usage Cited in: J Cell Physiol. 2019 Jan 26.

    Western blot analysis was used to confirm the cytoplasmic and nuclear protein expression of β-catenin and AR in the LNCaP, DRCaP, BRCaP, and ERCaP cells treated with the wnt/β-catenin activator (AZD2858, 5 nM, 48 hr) or the wnt/β-catenin inhibitor (PNU74654, 129.8 μM, 48 hr).

    View All GSK-3 Isoform Specific Products:

    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    AZD2858 is a potent, orally active GSK-3 inhibitor, with IC50s of 0.9 and 5 nM for GSK-3α and GSK-3β, respectively, used in the research of fracture healing.

    IC50 & Target[4]

    GSK-3α

    0.9 nM (IC50)

    GSK-3β

    5 nM (IC50)

    CDK5/p25

    356 nM (IC50)

    Haspin

    366 nM (IC50)

    CDK5/p35

    387 nM (IC50)

    DYRK2

    491 nM (IC50)

    CDK2/cyclin A

    810 nM (IC50)

    CDK1/cyclin B

    1246 nM (IC50)

    PIM3

    1269 nM (IC50)

    TLK2

    1381 nM (IC50)

    PKD2

    2462 nM (IC50)

    CDK2/cyclin E

    3310 nM (IC50)

    Aurora-A

    4966 nM (IC50)

    In Vitro

    AZD2858 (1 μM) increases β-catenin levels after a short period of time in human osteoblast cells. AZD2858 inhibits GSK-3β dependent phosphorylation with an IC50 of 68 nM. AZD2858 (10 nM) has no effect on β-catenin levels[1]. AZD2858 increases TAZ expression and osterix expression both by 1.4-fold, with EC50 of 440 nM and 1.2 μM, respectively, in hADSC. AZD2858 also induces a marked increase in osteogenic mineralisation in hADSC[3]. AZD2858 (AR28) demonstrates from 70- to greater than 6000-fold selectivity over a panel of other kinases and an IC50 of 5 nM. AR28 inhibits GSK-3 in murine cells and indicates activation of the canonical Wnt/β-catenin signaling cascade. AR28 (50, 10, and 1 nM) enhances the clonogenic ability of mesenchymal progenitors with osteogenic and adipogenic potential. AR28 (50 µM) also enhances the differentiation ability of mesenchymal progenitors to the osteogenic but not adipogenic lineage in vitro[4].

    In Vivo

    AZD2858 (20 mg/kg) causes a dose-dependent increase in trabecular bone mass compared to control after a two-week treatment with a maximum effect[1]. AZD2858 exhibits a substantial effect on fracture healing. AZD2858 (20 mg/kg) causes an increase in cortical BMC of 9%, cortical area of 10%, and cortical thickness of 11% at 3 weeks in the non-operated right femur of rats[2]. AZD2858 (30 μmol/kg/day) alters the biomarkers of bone turnover with statistically significant increases in P1NP and decreases in TRAcP-5b seen from 3 days of treatment and onwards. AZD2858 demonstrates significant changes in serum bone turnover markers (P1NP and TRAcP-5b) and femur bone formation after only 7 days of daily dosing[3]. AZD2858 (AR28, 30 mg/kg, s.c.) stimulates an increase in an initial wave of mesenchymal progenitors with osteogenic and adipogenic potential and drives their differentiation to the osteogenic lineage in BALB/c mice. AR28 (30 mg/kg, s.c.) enhances the proliferation of committed hematopoietic progenitors and their differentiation to the osteoclast lineage but does not prevent an overall increase in bone mass[4].

    Solvent & Solubility
    In Vitro: 

    DMSO : 12.5 mg/mL (27.56 mM; Need ultrasonic)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.2050 mL 11.0249 mL 22.0497 mL
    5 mM 0.4410 mL 2.2050 mL 4.4099 mL
    10 mM 0.2205 mL 1.1025 mL 2.2050 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: 1.25 mg/mL (2.76 mM); Suspended solution; Need ultrasonic

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: ≥ 1.25 mg/mL (2.76 mM); Clear solution

    References
    Kinase Assay
    [3]

    The potency of compounds at GSK-3β and cyclin-dependent protein kinase 2 (CDK2, kinase with closest homology to GSK-3β) is assessed using Z-LYTE™ Kinase assay kit in the presence of 7 and 80 μM ATP respectively. A ratiometric method is used to calculate the ratio of donor emission (445 nm) to acceptor emission (520 nm) after excitation of the donor fluorophore at 400 nm to quantitate the reaction progress. Kinase selectivity with AR79, AZD2858 and AZ13282107 are determined using the KinaseProfiler Service or University of Dundee Kinase. Over 80 different kinases are assessed at a single concentration of 1 or 10 μM of AR79, AZD2858 and AZ13282107. Concentration-inhibition 10-point curves to compounds that show activity are constructed to determine pIC50 estimations. Also, in some kinase assays these pIC50 estimations are converted to binding affinity values (pKi) using the Cheng-Prussoff equation to correct for the concentration of ATP used[3].

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

    Animal Administration
    [1]

    Each rat is dosed orally with vehicle or AZD2858 using a plastic gavage tube. The dose volume is 10 mL/kg. The vehicle consists of deionized water adjusted to pH 3.5±0.1. Formulations are adjusted to pH 3.5±0.1. The doses are 0, 0.2, 2 or 20 mg/kg respectively and administered either twice daily (TD), once daily (OD), every other day (O/2D), or every fourth day (O/4D) for 14 days. In total, the protocol results in 13 groups with 8 animals in each group (104 animals). At 7 days after the start of the study, and again 2 days prior to the scheduled terminal necropsy, each animal is injected subcutaneously with a bicarbonate buffered calcein solution (8 mg/kg, 1 mL/kg)[1].

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

    References
    Molecular Weight

    453.52

    Formula

    C₂₁H₂₃N₇O₃S

    CAS No.

    486424-20-8

    SMILES

    O=C(C1=NC(C2=CC=C(S(=O)(N3CCN(C)CC3)=O)C=C2)=CN=C1N)NC4=CC=CN=C4

    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

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    Product Name:
    AZD2858
    Cat. No.:
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    Cat. No.: HY-15761