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Drug-induced dyskinesia is a debilitating side effect induced by anti-parkinsonian and antipsychotic drugs. Frequency can reach 80% in Parkinson disease and around 50% in schizophrenia patients treated with typical antipsychotics. Treatments for dyskinesia currently available have a very limited impact and generate important side effects. We have identified a new pharmacological target that may offer a new perspective in the treatment of these conditions. The target is composed of two nuclear receptors involved in the modulation of gene expression. We developed a sensitive biosensor that can monitor the activity of this complex. We used this assay to screen library of compounds and identified novel molecules (hits) that interact with this cellular target.
In the work proposed in the current application, we will now generate small libraries of hit analogues (hit expansion) in order to improve properties as lead compounds. Lead compounds will then be tested in animal models of drug-induced dyskinesia.
Merck Canada Inc.
Biochemistry / Molecular biology
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