1. Cell Cycle/DNA Damage
  2. Polo-like Kinase (PLK)
  3. GSK461364

GSK461364  (Synonyms: GSK461364A)

Cat. No.: HY-50877 Purity: 99.20%
COA Handling Instructions

GSK461364 is a selective, reversible and ATP-competitive Polo-like kinase 1 (PLK1) inhibitor with a Ki value of 2.2 nM.

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

GSK461364 Chemical Structure

GSK461364 Chemical Structure

CAS No. : 929095-18-1

Size Price Stock Quantity
Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
USD 105 In-stock
Solution
10 mM * 1 mL in DMSO USD 105 In-stock
Solid
1 mg USD 41 In-stock
5 mg USD 88 In-stock
10 mg USD 165 In-stock
50 mg USD 528 In-stock
100 mg USD 792 In-stock
200 mg USD 1188 In-stock
500 mg   Get quote  
1 g   Get quote  

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This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 12 publication(s) in Google Scholar

Top Publications Citing Use of Products

    GSK461364 purchased from MedChemExpress. Usage Cited in: Eur J Cancer. 2013 Sep;49(14):3020-8.  [Abstract]

    Western blot analysis of PLK1 protein levels from GSK461364A treated U251 cells; actin levels are measured as a loading control.

    View All Polo-like Kinase (PLK) Isoform Specific Products:

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    GSK461364 is a selective, reversible and ATP-competitive Polo-like kinase 1 (PLK1) inhibitor with a Ki value of 2.2 nM.

    IC50 & Target[3]

    PLK1

    2.2 nM (Ki)

    In Vitro

    GSK461364 is a potent, selective, and reversible ATP-competitive Plk1 inhibitor (Ki, 2.2 nM) with at least 390-fold greater selectivity for Plk1 than for Plk2 and Plk3 and 1,000-fold greater selectivity than for a panel of 48 other kinases[1]. GSK461364 (GSK461364A, 250 nM) inhibiting plk1 causes prolonged mitotic delay, aberrant mitotic exit, and p53 activation in A549 and PL45 cells. Knockdown of p53 significantly enhances the sensitivity of the cells to GSK461364A (30 or 300 nM) in preventing outgrowth in A549 and NCI-H460 cells, compared with cells with nonsilencing control siRNA[2]. GSK461364 can inhibits cell growth of most proliferating cancer cell lines, and suppresses 89% of cancer cell line (66 of 74 lines) proliferation, with a GI50 (concentration required to inhibit 50% cell growth) of ≤100 nM. GSK461364 (GSK461364A, >20 nM) blocks cells in G2-M phase with reduction of cells in G1 phase of A549 lung carcinoma line. GSK461364 (10-250 nM) blocks cells in G2 and M phases of the cell cycle and causes M-phase caspase-3/caspase-7 activation in cancer cells[3]. GSK461364 (0.5-2 μM) decreases level of PLK1 and pCDC25C, and cuases a dose- and time-dependent increase in pHisH3, an indicator of mitotic arrest in OS cell lines[4].

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

    In Vivo

    GSK461364 (50 mg/kg) exhibits various degrees of tumor growth delay (TGD) in multiple xenograft tumor models by i.p. one dose every 2 days repeated twelve times (q2d×12)[1].

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

    Clinical Trial
    Molecular Weight

    543.60

    Formula

    C27H28F3N5O2S

    CAS No.
    Appearance

    Solid

    Color

    White to gray

    SMILES

    O=C(C(SC(N1C=NC2=CC=C(C=C12)CN3CCN(CC3)C)=C4)=C4O[C@@H](C5=CC=CC=C5C(F)(F)F)C)N

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    DMSO : 50 mg/mL (91.98 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.8396 mL 9.1979 mL 18.3959 mL
    5 mM 0.3679 mL 1.8396 mL 3.6792 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass
    =
    Concentration
    ×
    Volume
    ×
    Molecular Weight *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

    =
    Concentration (final)

    C2

    ×
    Volume (final)

    V2

    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

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

      Solubility: ≥ 2.5 mg/mL (4.60 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

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

      Solubility: ≥ 2.5 mg/mL (4.60 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

      Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.82%

    References
    Kinase Assay
    [3]

    Kinase reactions are performed in a final assay volume of 10 μL using the Z'-Lyte Assay kit (Ser/Thr peptide 16). Briefly, reactions contained 50 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 1 mM DTT, 0.01% Brij 35, 0.01 mg/mL casein, 200 μM ATP, 200 μM Polo Box peptide (NH2-MAGPMQS[pT]PLNGAKK-OH), and 6 nM recombinant Plk1 (H6-tev-PLK 1-603). Plk1 is preincubated for 60 min in the presence or absence of 0 to 1,000 nM GSK461364. Reactions are then initiated by the addition of 2 μM peptide. After 15 min at 23°C, reactions are quenched and processed according the Z'-Lyte protocol and read on an plate reader. Raw fluorescence values are converted to concentration of product formed using substrate and product standards. IC50 values are determined using a two-parameter fit (Hill coefficient and IC50) using GraFit software. Because the potency of inhibition for GSK461364 is observed to vary as a function of the ATP concentration in a manner consistent with an ATP-competitive mode of inhibition, an upper limit for the Ki*app for GSK461364 is determined by applying the Cheng-Prusoff relationship for a competitive inhibitor (ATP Km*app=16 μM) to the IC50 value obtained with 60 min preincubation of GSK461364.

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

    Cell Assay
    [3]

    Cell lines grow in the recommended media at 37°C, 5% CO2 in a humidified incubator. Cells are plated in triplicate 96-well microtiter plates at 1,000 cells per well in culture media. GSK461364 (GSK461364A) dissolved in DMSO or negative control (0.1% DMSO) are added the following day, and one plate is harvested with 50 μL of CellTiter-Glo for a time 0 (T=0) measurement.

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

    Animal Administration
    [3]

    Cells are implanted in Nude mice and grown as tumor xenografts. Dosing began when tumors achieve appr 100 mm3. GSK461364 (GSK461364A) or the vehicle [4% DMA/Cremaphore (50:50), pH 5.6] is given i.p. to mice every 2 d (q2d×6, q2d×12) or every 4 d (q4d×3) at nominal dose levels of 25, 50, and 100 mg/kg/dose. Results are reported as median tumor volume for n=7 to 8 mice. Paclitaxel (30 mg/kg i.v.; q4d×3) is used as a positive control for comparison. Tumors are measured thrice a week with Vernier calipers, and tumor volume is calculated from two-dimensional measurements using an equation approximating the volume of a prolate ellipsoid [tumor volume mm3=(length × width2) × 0.5]. The maximum tolerated dose is defined as the highest dose that produces >20% mortality or >20% weight loss (appr 4 g). Antitumor activity is defined as tumor growth delay (TGD), partial regression (PR), or complete regression (CR). TGD represents the time differential between the treated and control tumors to reach a predetermined tumor volume of 1,000 mm3. PR is defined as a decrease in an individual tumor volume to one-half the initial starting volume for at least 1 wk (three consecutive measurements). CR is defined as a decrease in an individual tumor volume to <13 mm3 for at least 1 wk.

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

    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.8396 mL 9.1979 mL 18.3959 mL 45.9897 mL
    5 mM 0.3679 mL 1.8396 mL 3.6792 mL 9.1979 mL
    10 mM 0.1840 mL 0.9198 mL 1.8396 mL 4.5990 mL
    15 mM 0.1226 mL 0.6132 mL 1.2264 mL 3.0660 mL
    20 mM 0.0920 mL 0.4599 mL 0.9198 mL 2.2995 mL
    25 mM 0.0736 mL 0.3679 mL 0.7358 mL 1.8396 mL
    30 mM 0.0613 mL 0.3066 mL 0.6132 mL 1.5330 mL
    40 mM 0.0460 mL 0.2299 mL 0.4599 mL 1.1497 mL
    50 mM 0.0368 mL 0.1840 mL 0.3679 mL 0.9198 mL
    60 mM 0.0307 mL 0.1533 mL 0.3066 mL 0.7665 mL
    80 mM 0.0230 mL 0.1150 mL 0.2299 mL 0.5749 mL
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    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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