1. Cell Cycle/DNA Damage
  2. CDK

AZD-5438 

Cat. No.: HY-10012 Purity: 99.84%
Handling Instructions

AZD-5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM in cell-free assays. AZD-5438 shows less inhibition activity against GSK3β, CDK5 and CDK6.

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

AZD-5438 Chemical Structure

AZD-5438 Chemical Structure

CAS No. : 602306-29-6

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 79 In-stock
Estimated Time of Arrival: December 31
10 mg USD 72 In-stock
Estimated Time of Arrival: December 31
50 mg USD 216 In-stock
Estimated Time of Arrival: December 31
100 mg USD 384 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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    AZD-5438 purchased from MCE. Usage Cited in: Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.

    Western blot analysis of selected MAPK and AKT/mTOR pathway components in Trametinib- and Temsirolimus-treated cells.

    AZD-5438 purchased from MCE. Usage Cited in: Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.

    Western blot analysis of selected MAPK and AKT/mTOR pathway components in Trametinib- and Temsirolimus-treated cells.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    AZD-5438 is a potent inhibitor of CDK1/2/9 with IC50 of 16 nM/6 nM/20 nM in cell-free assays. AZD-5438 shows less inhibition activity against GSK3β, CDK5 and CDK6.

    IC50 & Target

    cdk2-cyclin E

    6 nM (IC50)

    cdk2-cyclin A

    45 nM (IC50)

    cdk5-p25

    14 nM (IC50)

    cdk1-cyclin B1

    16 nM (IC50)

    cdk9-cyclin T

    20 nM (IC50)

    cdk6-cyclin D3

    21 nM (IC50)

    cdk4-cyclin D1

    449 nM (IC50)

    cdk7-cyclin H

    821 nM (IC50)

    In Vitro

    AZD5438 potently inhibits the kinase activity of cyclin E-cdk2, cyclin A-cdk2, cyclin B1-cdk1, p25-cdk5, cyclin D3-cdk6, and cyclin T-cdk9 (IC50, 6, 45, 16, 21, and 20 nM, respectively). AZD5438 potently inhibits the kinase activity of cyclin E-cdk2, cyclin A-cdk2, cyclin B1-cdk1, p25-cdk5, cyclin D3-cdk6, and cyclin T-cdk9 (IC50, 6, 45, 16, 21, and 20 nM, respectively). In common with many other cdk inhibitors, AZD5438 also inhibits the kinase activity of p25-cdk5 and glycogen synthase kinase 3β in vitro (IC50, 14 and 17 nM, respectively)[1]. AZD5438 significantly augments cellular radiosensitivity in NSCLC cells. Combined treatment with AZD5438 and irradiation also enhances tumor growth delay, with an enhancement factor ranging from 1.2-1.7[2].

    In Vivo

    AZD5438 (50 mg/kg twice daily or 75 mg/kg, p.o.) inhibits human tumor xenograft growth. In vivo, AZD5438 reduces the proportion of actively cycling cells. Further pharmacodynamic analysis of AZD5438-treated SW620 xenografts shows that efficacious doses of AZD5438 (>40% tumor growth inhibition) maintains suppression of biomarkers, such as phospho-pRbSer249/Thr252, for up to 16 hours following a single oral dose[1].

    Clinical Trial
    Solvent & Solubility
    In Vitro: 

    DMSO : 100 mg/mL (269.21 mM; Need ultrasonic)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.6921 mL 13.4604 mL 26.9208 mL
    5 mM 0.5384 mL 2.6921 mL 5.3842 mL
    10 mM 0.2692 mL 1.3460 mL 2.6921 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

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

      Solubility: ≥ 2.5 mg/mL (6.73 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (6.73 mM); Clear solution

    • 3.

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

      Solubility: ≥ 2.5 mg/mL (6.73 mM); Clear solution

    References
    Cell Assay
    [1]

    AZD5438 is tested against solid tumor cell lines as previously described. Briefly, cells are incubated for 48 h with AZD5438 at a range of concentrations. At the end of incubation, the cells are pulsed with 5-bromo-2'-deoxyuridine (BrdUrd) and the amount of DNA synthesis is measured. The IC50 for inhibition of proliferation is specifically determined independently of cell death. Multiple myeloma cell lines are seeded into 96-well plates in RPMI 1640 supplemented with 10% FCS and glutamine and dosed with AZD5438 for 72 h. Cell growth is measured using AlamarBlue and GI50 values are calculated with reference to pretreatment control values.

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

    Animal Administration
    [1]

    All human tumor xenografts except HX147 are established by s.c. injecting 100 μL of tumor cells (between 1×106 and 1×107 cells mixed 1:1 with Matrigel). HX147 tumors are derived from fragment implants (1 mm3 pieces) from tumors taken from mice initially implanted s.c. with 1×107 cells. These tumor fragments are passaged in mice thrice before implant for antitumor work. Tumors are measured up to three times per week with calipers, tumor volumes are calculated, and the data are plotted as geometric mean for each group versus time, as previously described. Animals are randomized into treatment groups (typically n=10) when tumors reach a mean size of approximately >0.2 cm3 and >0.5 cm3 for mice and rats, respectively. AZD5438 is prepared in hydroxy-propyl-methyl-cellulose. Animals are given either AZD5438 (37.5-75 mg/kg) or vehicle control once or twice daily by oral gavage for appr 3 wk in each case. Tumor volume and percentage tumor growth inhibition (% TGI) are calculated as described previously. Statistical analysis of any change in tumor volume is carried out using a standard t test (P<0.05 is considered to be statistically significant).

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

    References
    Molecular Weight

    371.46

    Formula

    C₁₈H₂₁N₅O₂S

    CAS No.

    602306-29-6

    SMILES

    O=S(C1=CC=C(NC2=NC(C3=CN=C(N3C(C)C)C)=CC=N2)C=C1)(C)=O

    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:
    AZD-5438
    Cat. No.:
    HY-10012
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    AZD-5438

    Cat. No.: HY-10012