Home Cell Cycle PLK inhibitor GW843682X

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GW843682X PLK inhibitor

Cat.No.S2880

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 PLK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 477.46

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

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

Chemical Information, Storage & Stability

Molecular Weight 477.46 Formula

C22H18F3N3O4S

 Storage (From the date of receipt)
CAS No. 660868-91-7 Download SDF Storage of Stock Solutions

Solubility

In vitro
Batch:

DMSO : 95 mg/mL (198.96 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Mechanism of Action

Targets/IC50/Ki
PLK1 [1]
(in MTT assay)
2.2 nM
PLK3 [1]
(in MTT assay)
9.1 nM
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
References
  • [4] https://pubmed.ncbi.nlm.nih.gov/22621898/
  • [5] https://pubmed.ncbi.nlm.nih.gov/19421227/

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