LabAutomation 2006 - SLAS

LabAutomation2006
10:30 am Wednesday, January 25, 2006 Track 3: High-Throughput Technologies Room: Learning Center
Wyndham Palm Springs Hotel
Zhong Zhong
Co-Author(s)
Cell & Molecular Technologies, Inc.
Natalie Fursov, Cell & Molecular Technologies, Inc.
Phillipsburg, New Jersey
zzhong@cmt-inc.net
Kevin Lee. Sentigen Biosciences
Mark Federici, Roland Tacke, Tom Livelli
Cell & Molecular Technologies, Inc.
Rapid Evaluation of Compounds’ Off-Target Activities Against GPCRs by Tango Assay
System, a Novel Reporter Technology
We have developed a new G-protein coupled receptors (GPCR) profiling panel based on Sentigen Biosciences’ TangoTM Assay System.
Unlike conventional compound selectivity services that utilize biochemical or membrane binding methods, the Tango Assay Profiling system
employs a functional cell-based assay that provides information about efficacy and agonism/antagonism properties. A large cryopreserved
cell bank has been set up in which each cell type expresses one of the 54 selected GPCRs in conjunction with Tango Assay components.
We demonstrated that we can thaw cells from the cell bank to generate custom panels on demand to profile agonism/antagonism
activities of compounds on an array of GPCRs.
Activation of GPCR signaling is in general tightly coupled with subsequent receptor desensitization, a process mediated by the recruitment
of intracellular arrestin proteins to the activated receptor. Tango is a luciferase-based chemiluminescent assay that detects ligand-induced
activation/inactivation of target receptor by quantitatively measuring its interaction with arrestin. The assay design does not depend on
knowledge of the G-protein signaling specificity of the target receptor. In addition, Tango Assay System permits the selective interrogation
of the specific target receptor, and is not affected by signaling mediated by endogenous receptors. The high sensitivity of the assay allows
detection of receptor-ligand interactions without the need of over-expressing target receptor or singaling components. We will present data
to demonstrate that the Tango assays are broadly applicable to all classes of GPCRs. Assays’ homogeneous format and simple workflow
make it ideal for GPCR panel profiling.
10:30 am Monday, January 23, 2006 Track 4: Informatics Room: Madera
Wyndham Palm Springs Hotel
John Davies
Novartis
Cambridge, Massachusetts
john-W.davies@novartis.com
An Holistic Approach to HTS Data Triaging
A number of companies today are trying to offset attrition rates in the drug discovery process by simply widening their pipeline. Companies
are now running more screens with larger collections of compounds than they have ever done before. This is creating a vast amount of
HTS data which often, but not always, feeds into an automated IT analysis platform. At this stage little, if anything, is done to analyze and
triage the entire data set. Even less is done to apply orthogonal data mining methods which can increase SAR knowledge. We will show
a number of different approaches we have employed to analyze large-scale HTS data for the purposes of increasing its intrinsic chemical
and biological information content.
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