Horizon eBook - 12

Innovations in Cell-Based Screening * More Predictive Cell-Based Assays

Profiling Signaling Pathways

The cell-based assay, a mainstay of drug discovery,
keeps improving. Advances include a greater
emphasis on primary cells and more automation.


| GENengnews.com

According to Maite Romier, a research and
development project leader at Cisbio Bioassays,
"We chose to develop the new HTRF
(homogenous time-resolved fluorescence) assay as
part of our innovation efforts to provide cell-based
solutions for phosphoproteins, and for cell signaling
pathway investigation in general."
The HTRF platform is a complete, wellestablished assay system that already covers 10 major
pathways. Based on an "add and read" homogenous
protocol-a robust alternative to ELISA or beadbased technologies-HTRF "simply enables a fast
analysis of what's happening in the cell."
"Specifically, the cell-based phospho/total
beta-catenin assay was undertaken to allow the
investigation of the Wnt signaling pathway, an
area of growing interest for drug discovery

researchers," continues Romier. "Wnt signaling
controls the phosphorylation status of betacatenin, a critical regulator and key protein
in the pathway. This assay serves as a pathway
readout when trying to modulate the pathway
in the disease state.
"Total beta-catenin is an important cotranscriptional activator of many significant genes
involved in differentiation, development, cell
proliferation, and hence cancer. Our results showed
that the assay can distinguish between pools of
cellular endogenous beta-catenin whether
phosphorylated or not, which have different
important functions in cell signaling. Screening
for compounds using the beta-catenin assay
seems very promising for discovering new drug
mechanisms in the cancer field."


Horizon eBook

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