ChemMine. A Compound Mining Database for Chemical Genomics

Chemical genomics is a promising new technology for studying gene functions in the context of living organisms or cell systems. It complements existing molecular and genetics tools (e.g. mutagenesis, RNAi) by allowing fine-tunable in vivo modulations of protein functions and cellular processes (Blackwell and Zhao, 2003; Austin et al., 2004; Lipinski and Hopkins, 2004). This approach is feasible because of recent advances in the synthesis of large libraries of small chemicals. In chemical genomics experiments the libraries are used to identify in high-throughput screens interesting agonistic or antagonistic candidates that interfere with a biological process of interest. Typically, the libraries, used in these screens, consist of collections of diverse compounds with predicted drug-like properties (Lipinski et al., 1997; Oprea and Gottfries, 2001; Oprea, 2002; Baurin et al., 2004; Stockwell, 2004). In analogy to genetic screens, chemical genomic screens can utilize forward and reverse strategies (Schreiber, 1998; Haggarty et al., 2003). Forward chemical genomics screens probe modulations of complex biological processes rather than isolated targets. This is in contrast to small molecule discovery in the pharmaceutical and agricultural industry where the drug-able target is usually known and screened using in vitro systems. To fully understand the mode of action of isolated compounds with interesting biological activities, it is frequently necessary to identify their target(s) at a later stage of a screening project using biochemical and genetics gene or protein isolation techniques. In contrast to this forward strategy, reverse chemical genomics screens resemble, in their initial stage, drug discovery approaches by screening known targets (Drews, 2000). Subsequently, the isolated bioactive chemicals are used to study the molecular and biological functions of poorly characterized proteins in vivo. Both forward and reverse approaches utilize the identified chemicals as “research tools” for determining the functions, interactions, and architecture of cellular networks in living organisms. A potential pharmaceutical or agricultural application can be of interest but is not the central goal of this technology.