Home Cell Cycle PLK inhibitor GW843682X For research use only.

GW843682X

GW843682X is a selective, ATP-competitive inhibitor of PLK1 and PLK3, with IC50s of 2.2 nM and 9.1 nM, respectively, and is also >100-fold selective against ~30 other kinases.

GW843682X Chemical Structure

GW843682X Chemical Structure

CAS: 660868-91-7

Purity & Quality Control

Batch: S288001 DMSO] 95 mg/mL] false] Ethanol] 3 mg/mL] false] Water] Insoluble] false Purity: 99.96%
99.96

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Biological Activity

Description GW843682X is a selective, ATP-competitive inhibitor of PLK1 and PLK3, with IC50s of 2.2 nM and 9.1 nM, respectively, and is also >100-fold selective against ~30 other kinases.
Targets
PLK1 [1]
(in MTT assay)		 PLK3 [1]
(in MTT assay)
2.2 nM 9.1 nM
In vitro
In vitro

GW 843682X is a submicromolar inhibitor of proliferation of most tumor cells in culture, a notable exception being PC-3, a prostate carcinoma cell line. GW 843682X is also selective for tumor cells compared with normal diploid fibroblasts (HDF), with >10-fold difference in potency. GW 843682X is equipotent (∼200 nmol/L) against MES-SA/DX5 and the parental line MES-SA, suggesting that the compound is not effectively removed by the P-glycoprotein efflux pump in the cell. GW 843682X dose-dependently inhibits the phosphorylation of Ser15-p53 by PLK1 in HeLa cells expressing the tet-inducible chimeric p53-PLK1 protein. GW 843682X enhances HDF cell outgrowth with 30% at 3.3 μM and is able to enhance H460 outgrowth at lowest concentration of 0.37 μM. GW 843682X results in a strong G2-M arrest at 3 μM and very little G2-M arrest is observed at 1 μM in HDF cells. GW 843682X (3 μM) shows a reduced G2-M arrest, but there is an increase in sub-2N DNA content in H460 cells. GW 843682X (0.5 μM) results in cells that are larger in size than the untreated H460 cells and has multiple nuclei. [1] GW 843682X inhibits PLK1, PLK2, PLK3 and PLK4 with Ki values of 4.8 nM, 3.8 nM, 8 nM and 0.163 μM, respectively. [2] GW 843682X (1 μM) interferes with the localization of endogenous MyoGEF at the central spindle in HeLa cells. GW 843682X (1 μM) disrupts the localization of GFP-MyoGEF-wt (GFP-WT), GFP-MyoGEF-T574A (GFP-T574A), and GFP-MyoGEF-T574E (GFP-T574E) to the central spindle in HeLa cell. [3] GW-843682X causes identical premature midzone assembly and protein recruitment, suggesting that the drug effect is specific to Plk1 inhibition. GW 843682X (200 nM) causes microtubule bundling and central spindlin and PRC1 recruitments in equator in HeLa cells. [4]
Kinase Assay In vitro Kinase Assays
PLK1 and PLK3 are added to white 384-well assay plates at variable known concentrations in 100% DMSO. DMSO (1–5% final) and EDTA (65 mM) are used as controls. Reaction Mix contains the following components at 22°C: 25 mM HEPES (pH 7.2); 15 mM MgCl2; 1 μM ATP; 0.05 μCi/well [γ-33P]ATP (10 Ci/mmol); 1 μM substrate peptide; 0.15 mg/mL bovine serum albumin; 1 mM DTT; and 2 nM PLK1 kinase domain or 5 nM full-length PLK3. Reaction Mix (10 or 20 μL) is quickly added to each well immediately following addition of enzyme via automated liquid handlers and incubated for 1 to 1.5 h at 22°C. The 20 μL enzymatic reactions are stopped with 50 μL of stop mix [50 mM EDTA, 4.0 mg/mL streptavidin SPA beads in Dulbecco
Cell Research Cell lines H460 and HDF cells
Concentrations 3 μM
Incubation Time 72 hours
Method

H460 cells are plated at a density of 2×103 per well, HDF cells are plated at 5×103 per well, and the drug-resistant cell line MES-SA/DX5 and its sensitive parent line MES-SA are plated at 7×103 and 6×103 per well, respectively, in a 96-well plate. These densities allow vehicle controls to grow logarithmically during the course of the 3-day assay. All cells are exposed to 3-fold dilutions of GW 843682X (30–0.00152 μM) in low-glucose DMEM containing 5% FBS, 50 μg/mL gentamicin, and 0.3% (v/v) DMSO (HDF cells); RPMI 1640 containing 5% FBS, 50 μg/mL gentamicin, and 0.3% (v/v) DMSO (H460); or McCoy's 5A containing 5% FBS, 50 μg/mL gentamicin, and 0.3% (v/v) DMSO (MES-SA and MES-SA/DX5).

Chemical Information & Solubility

Molecular Weight 477.46 Formula

C22H18F3N3O4S
CAS No. 660868-91-7 SDF Download GW843682X SDF
Smiles COC1=C(OC)C=C2[N](C=NC2=C1)C3=CC(=C(S3)C(N)=O)OCC4=C(C=CC=C4)C(F)(F)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 95 mg/mL ( (198.96 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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