General presentation:
Important drug targets today are the metabotropic glutamate receptors (mGluRs). These receptors have been linked with neurological and
psychiatric disorders such as absence epilepsy, anxiety, depression, migraine, Parkinsons disease and pain, but no drugs are currently
available the market although many are in pre-clinical trials.
Screening modulators of mGluRs has proven difficult. In particular, screening tools for mGlu3 (Schizophrenia) and mGlu7 (absence
epilepsy) are not existing.
In this proposal cellular high-throughput (HTS) assay kits for the detection of innovative mGlu modulators will be developed and
commercialized. These kits will be based on sensors using suicide enzymes that monitor the various conformational states of the receptors
by TR-FRET. This will allow the direct monitoring of types of mGluRs ligands including agonists, antagonists, partial agonists, positive (PAM)
or negative allosteric modulators (NAM).
Our idea is to develop a ready to use cellular sensor-based assay kit for each mGluR. The easiness of use of these new kits will allow a
large number of pharmaceutical companies to launch new HTS programs on these very difficult targets. Moreover these innovative utilities
will possibly persuade hesitant companies to enter this market.
The collaboration has already proven fruitful in developing TR-FRET tools in order to realize the proof-of-concept of a ligand binding assay
for the mGlu2 receptor. In one experiment it is possible to define whether the modulator is an agonist, antagonist, partial agonist, positive
(PAM) or negative allosteric modulator (NAM) and determine their binding constants. A unique concept that merits to be developed into
products.
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Help of the ANR 0 euros
Beginning and duration of the scientific project:
- 0 Months
