Abstract
Chemical genomics is a new research paradigm with importantapplications in drug discovery. It links genomic targets withsmall-molecule chemistries thereby allowing for efficient targetvalidation and lead compound identification. ACADIA'schemical-genomics platform consists of a large and diverse small-moleculelibrary (800,000), a reference drug library (2,000), druggablegenomic targets (>300) and a cell-based functional assaytechnology (R-SAT(TM); Receptor Selection and AmplificationTechnology) that allows for ultra-high throughput screening(>500,000 data points/week) as well as high throughputpharmacology and profiling over a wide range of targets. Twoexamples are presented that illustrate the success of ourchemical-genomics approach: (i) The validation of inverse agonismat serotonin 5-HT(2A) receptors as an antipsychotic mechanismand the subsequent discovery of potent and selectively acting 5-HT(2A) inverse agonists, currently in preclinical development,and (ii) the discovery of the first ectopically binding subtype-selective muscarinic m1 agonist.
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