Biomedical Engineering Reference
In-Depth Information
10
CHEMOINFORMATIC
CHARACTERIZATION OF THE
CHEMICAL SPACE AND MOLECULAR
DIVERSITY OF COMPOUND
LIBRARIES
JOSE LUIS MEDINA-FRANCO
10.1
INTRODUCTION
Drug discovery campaigns frequently involve chemical libraries from a variety of
sources, including combinatorial libraries [1,2], commercial vendor compounds, nat-
ural products [3], and other collections, which may contain hundreds, thousands, or
even millions of compounds. Such databases can be used for a wide variety of tasks,
such as the development and exploration of structure-activity relationships (SARs)
[4] and the identification of polypharmacology [5]. The type of screening library
utilized should be closely associated with the objective of the particular screening
campaign [6]. Chemically diverse libraries are particularly attractive for identifying
novel scaffolds for new or relatively unexplored targets. If the goal of the screen-
ing is directed to a specific target family, one may use target-oriented synthesis
(TOS) [7], focused, or targeted libraries [8]. If the goal is lead optimization, chemical
libraries with high intermolecular similarity (i.e., highly dense libraries) are an attrac-
tive source. In this regard, natural products have unique characteristics attractive for
drug discovery [3,9]. For example, the chemical structures of natural products are,
