GW843682, 5-(5,6-Dimethoxy-1H-benzimidazol-1-yl)-3-{[2-(trifluoromethyl)-benzyl]oxy}thiophene-2-carboxamide Chemical Properties

Boiling point:

609.1±65.0 °C(Predicted)

Density 

1.45±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: >10mg/mL

pka

15.03±0.50(Predicted)

form 

solid

color 

off-white

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36/37

WGK Germany 

3

GW843682, 5-(5,6-Dimethoxy-1H-benzimidazol-1-yl)-3-{[2-(trifluoromethyl)-benzyl]oxy}thiophene-2-carboxamide Usage And Synthesis

Description

GW843682X is a reversible, cell-permeable polo-like kinase (PLK) inhibitor. It selectively inhibits Plk1 and Plk3 (IC₅₀s = 2.2 and 9.1 nM, respectively) over PDGFR1β, VEGFR2, Aurora A, and Cdk2/cyclin A (IC₅₀s = 160, 360, 4,800, and 7,600 nM, respectively), as well as over 30 other kinases, in a cell-free assay. GW843682X also inhibits Plk1 activity in vitro in HeLa cells (IC₅₀ = 0.14 μM in a reporter assay using chimeric Plk1). It inhibits growth in nine cancer cell lines in a panel (IC₅₀s = 0.11-0.7 μM) but not of PC3 human prostate cancer cells (IC₅₀ = 6.82 μM) or non-cancerous human diploid fibroblasts (HDFs; IC₅₀ = 6.14 μM). GW843682X inhibits growth of MES-SA human uterine sarcoma cells, as well as of the drug-resistant, P-glycoprotein-expressing MES-SA/Dx5 subline (IC₅₀s = 0.21 and 0.21 μM, respectively). It also inhibits the growth of patient-derived leukemia cells (IC₅₀s = <0.25-0.8 μM). GW843682X induces G₂/M cell cycle arrest and apoptosis of H460 human lung and PALL-2 and MOLM13 human leukemia cancer cells in a concentration-dependent manner.

Uses

GW843682X is a polo-like kinase-1 (PLK1) and polo-like kinase-3 (PLK3) inhibitor.

Definition

ChEBI: 5-(5,6-dimethoxy-1-benzimidazolyl)-3-[[2-(trifluoromethyl)phenyl]methoxy]-2-thiophenecarboxamide is a member of (trifluoromethyl)benzenes.

Biological Activity

Selective inhibitor of polo-like kinase 1 (PLK1) and polo-like kinase 3 (PLK3) (IC 50 values are 2.2 and 9.1 nM respectively). Displays > 100-fold selectivity over ~30 other kinases tested including cdk1 and cdk2. Inhibits proliferation of most tumor cells in vitro and is selective over normal diploid fibroblasts.

storage

Desiccate at +4°C

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