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Informatics‐driven, fragment‐based drug discovery and refinement engine coupled with integrative pharmacology screens effectively prioritizes novel CNS experimental therapeutic selection
Author(s) -
Chico Laura K,
Watterson D. Martin
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.910.1
Subject(s) - drug discovery , informatics , computer science , leverage (statistics) , chemical space , computational biology , data science , bioinformatics , biology , artificial intelligence , engineering , electrical engineering
Adequate penetration of the blood brain barrier and avoidance of CYP2D6 substrates represents major challenges to success in the discovery of new molecular entities for CNS disorders. Thus, we sought to develop and validate a rapid, novel small molecule discovery engine for CNS experimental therapeutics characterized by front end designs that leverage trends from in‐house databases and informatics analyses and incorporate facile, high‐yield synthetic chemistry paradigms to sample diverse chemical space. The recursive nature of this platform permits the integration of pharmacological screens to focus on novel compounds with a high potential for success in later preclinical evaluation for investigational new drug (IND) status as a driving force for medicinal chemistry refinement. Additionally, the flexible nature of the discovery engine allowed for application to both function and single molecular target discovery campaigns. Commercial development of candidates emerging from this platform provides validation, as well as feedback for future optimization. Progress on preclinical and commercial development will be reported along with trends that have the potential for application to diverse chemotypes and targets.