In vivo phenotypic drug discovery: applying a behavioral assay to the discovery and optimization of novel antipsychotic agents12. Issue 6 (10th May 2016)

• Record Type: Journal Article
• Authors: Shao, Liming; Campbell, Una C.; Fang, Q. Kevin; Powell, Noel A.; Campbell, John E.; Jones, Philip G.; Hanania, Taleen; Alexandrov, Vadim; Morganstern, Irene; Sabath, Emily; Zhong, Hua M.; Large, Thomas H.; Spear, Kerry L.
• Is Part Of: MedChemComm. Volume 7:Issue 6(2016:Jun.)
• Page Start: 1093
• Page End: 1101
• Publication Date: 2016-05-10
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c6md00128a
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : A mouse-based assay (SmartCube) was used for both screening and lead optimization of a novel antipsychotic. Abstract : Phenotypic drug discovery (PDD) is increasingly being recognized as a viable compliment to target-based drug discovery (TDD). By measuring functional changes, typically at a systems level, PDD can facilitate the identification of compounds having a desirable pharmacology. This capability is particularly important when studying CNS diseases where drug efficacy may require modulation of multiple targets in order to overcome a robust, adaptive biological system. Here, we report the application of a mouse-based high-dimensional behavioral assay to the discovery and optimization of a structurally and mechanistically novel antipsychotic. Lead optimization focused on optimizing complex behavioral features and no explicit effort was made to identify the target (or targets) involved.