GPCR ligand screening assay Monitors the very early activation stage of Frizzled-Receptors of the GPCR group Our assay can be implemented in a cell-free chemical compound high-throughput target screening. GPCR is the largest known category of molecular targets with verified therapeutic value. Up to 40% of approved drugs are targeted to GPCRs. 25% of the top 200 best-selling drug targets are GPCRs.

1. Target Screening for Pharmaceuticals – cell-free GPCR drug discovery high-throughput screening
Pharmaceutical market INVENTION / Technology offer Your benefit
The top 20 players in pharmaceutical industry GPCR ligand screening assay • very simple & robust
had revenues of US$ 497,519 million in • upgrade for high throughput screening
2006. In 2005 a global market growth of 7 % Monitors the very early activation stage of • chemical compound library screening
was achieved. The pharmaceutical market is Frizzled-Receptors of the GPCR group. • monitoring very early activation GPCR
still expanding. stage
• cell-free : no side-effects
GPCRs (G protein-coupled receptor) take up
a significant share of drug development
pipeline across the pharmaceutical industry.
Monitors very early activation stage
We have established an assay which
GPCR Market monitors the very early stages of
• 25% of the top 200 best-selling drug Wnt/Frizzled activation - namely the
targets activation of trimeric G proteins in response
• 40% of approved drugs to Wnt ligand-induced activation of the
• Highest test turnover of 300.000 Frizzled receptors.
substances per day As 19 Wnt ligands and 10 Frizzled receptors
exist in humans, our assay can be targeted to
any of the particular Wnt/Frizzled pair and
GPCRs: 40 % of pharmaceutical targets thus be extremely specific for any particular
GPCR is the largest known category of case of pathological or physiological
molecular targets with verified therapeutic activation of the pathway.
value. Up to 40% of approved drugs are Furthermore, our assay can identify small
targeted to GPCRs. 25% of the top 200 best- molecules which do not need membrane
selling drug targets are GPCRs. permeability, thus markedly expanding the
GPCR ligand screening molecule repertoire from which to screen for
Screening for GPCR-targeted drugs thus is a agonists/antagonists serving as future drugs.
hot topic in pharmaceutical research. The
very high test turnover allows screening of GPCRs as talented all-rounders
300.000 substances per day (Bayer Health Involved in
Care). • Alzheimer
Patent Status: • Cancer
Chemical compound library screening • Schizophrenia
Our assay can be implemented in a cell-free The US Patent is granted, an European and • Virus, also tumor virus actions
chemical compound high-throughput target a US divisional patent application are • Stem cells
screening. currently pending. • All fundamental biological processes
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2. State of the Art Schizophrenia: Another pathological
The available platforms to screen for Wnt/Frizzled signaling pathways
consequence of overactivation of the
agonists/antagonists of the Wnt/Frizzled The Wnt/Frizzled signaling pathways are Wnt/Frizzled pathway is schizophrenia.
pathways mainly use cell culture-based highly conserved in animal evolution and
control multiple steps during organism Aging: Furthermore, whole-body activation
assays, where signal transduction is
monitored by activation of reporter constructs development. In the healthy adult, these of this pathway has been linked to aging.
placed under the beta-catenin-dependent pathways are mostly silent. Stem cells/organ regeneration: In contrast,
transcriptional regulation. activation of this pathway is necessary for the
proliferation of various types of stem cells
Disadvantages of the State of the Art (hematopoetic, neuronal, embryonic, etc) and
The disadvantage of this assay is that it is has been shown necessary for organ
prone to identify agents acting at the regeneration.
downstream levels of signaling, which are Alzheimer: Inhibition of this pathway has
conserved among multiple Wnt/Frizzled sub- also been implicated in the beta-amyloid
pathways - and thus lacking selectivity toxicity in Alzheimer’s disease.
amongst this multitude of pathways.
• State of the Art: cell culture-based Selected rerefence
Koval A, Purvanov V, Egger-Adam D,
assays,disadvantage: lacking selectivity Katanaev VL. (2011) Yellow Submarine of
The physiological and pathological
• Invention: cell-free & specific the Wnt/Frizzled Signaling: Submerging from
exceptions of this silence are of the
the G Protein Harbor to the Targets.
paramount medical importance.
Biochemical Pharmacology 82: 1311-1319.
INVENTION: Candidates for the treatment of Alzheimer,
Cancer, Schizophrenia
Frizzled GPCR ligand screening assay Thus, both agonists (activators) and Technology Transfer
antagonists (inhibitors) of the Wnt/Frizzled The Technologie-Lizenz-Büro GmbH is
The assay is very simple and robust. It pathway are highly demanded as therapeutic charged with the commercialization of this
comprises recombinant human Wnt ligands agents, the first being candidates for the techology and now offers companies the
and Frizzled receptors, bovine G proteins, regenerative medicine and anti-Alzheimer’s opportunity to enter into a cooperation and/or
and guanine nucleotide analogs modified for drugs, as well as agents for in vitro stem cell licensing agreement
time-resolved fluorescence (usage of other proliferation; the antagonists being
ways of labeling guanine nucleotide analogs candidates for the anti-cancer drugs, as well Contact: Andrea Nestl, PhD
such as for radioactive or fluorescent as anti-schizophrenia agents, and even “pills nestl@tlb.de
measurements is also possible). of youth”. Technology Licence Office (TLB) GmbH
In a high-throughput format, chemical Cancer: Inappropriate activation of the of the Universities in Baden-Württemberg,
libraries are added to the assay to screen for Wnt/Frizzled pathways leads to Ettlinger Straße 25, 76137 Karlsruhe,
antagonists of the Wnt/Frizzled-induced cancerogenesis in all tissues; the most Germany
activation of G proteins, or for agonists of prominent examples are the colon cancer Tel +49 721 79004-0, Fax +49 721 79004-79
Frizzled receptors (which would activate the (ca. 80% of cases due to overactivation of www.tlb.de, http://twitter.com/TLBGmbh
G proteins in the absence of Wnt ligands but the pathway) and breast cancer (ca. 50% of http://de-de.facebook.com/TLBGmbH
presence of Frizzled receptors). cases due to overactivation of the pathway).
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