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

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

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36/37

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

H413May cause long lasting harmful effects to aquatic life

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

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

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