title: Balancing novelty with confined chemical space in modern drug discovery.
abstract: BACKGROUND
  The concept of chemical space has broad applications in drug discovery. In response to the needs of drug discovery campaigns, different approaches are followed to efficiently populate, mine and select relevant chemical spaces that overlap with biologically relevant chemical spaces.
  
  
  METHODS
  This paper reviews major trends in current drug discovery and their impact on the mining and population of chemical space. We also survey different approaches to develop screening libraries with confined chemical spaces balancing physicochemical properties. In this context, the confinement is guided by criteria that can be divided in two broad categories: i) library design focused on a relevant therapeutic target or disease and ii) library design focused on the chemistry or a desired molecular function.
  
  
  CONCLUSIONS
  The design and development of chemical libraries should be associated with the specific purpose of the library and the project goals. The high complexity of drug discovery and the inherent imperfection of individual experimental and computational technologies prompt the integration of complementary library design and screening approaches to expedite the identification of new and better drugs. Library design approaches including diversity-oriented synthesis, biological-oriented synthesis or combinatorial library design, to name a few, and the design of focused libraries driven by target/disease, chemical structure or molecular function are more efficient if they are guided by multi-parameter optimization. In this context, consideration of pharmaceutically relevant properties is essential for balancing novelty with chemical space in drug discovery.
authors.affiliation: Mayo Clinic , 13400 East Shea Boulevard, Scottsdale, AZ 85259 , USA +1 480 301 4773 ; +1 480 301 9162 ; MedinaFranco.Jose@mayo.edu.
authors.forename: José L
authors.initials: JL
authors.lastname: Medina-Franco
authors.forename: Karina
authors.initials: K
authors.lastname: Martinez-Mayorga
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meurice
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000639:trends; D006801:Humans; D054852:Small Molecule Libraries
chemical_list: D054852:Small Molecule Libraries