Biologically active molecules that interact specifically with certain proteins or interfere with signalling pathways have tremendous value not only for the functional analysis of genes but also for drug development. Drug development is more and more influenced by new screening techniques to find biological active molecules. In forward chemical genetic screening approaches targets are not specified a priori. However, screening against the entire pathway eliminates any bias about what might score in the screen. Forward chemical genetic screens probe modulations of complex biological processes rather than isolated targets (Schreiber et al (2003) and De Palma et al (2004)). A forward chemical genetic screen can be applied to identify compounds that are capable of inhibiting certain biological functions of cells, such as the proliferation of cancer cells. Cancer is defined by any malignant growth or tumor caused by abnormal and uncontrolled cell division. Therefore, compounds that inhibit abnormal and uncontrolled cell division might be useful as therapeutic compounds. By utilizing this approach potent and selective inhibitors can be found that inhibit vital functions of cells, such as cancer cell proliferation and are suitable in the treatment of cancer.
In chemical genetics screens, small molecule libraries are used to identify in high-throughput screens interesting compounds that interfere with a certain biological function of a cell. Typically, the libraries, used in these screens, consist of collections of diverse compounds with predicted drug-like properties.
The discovery of novel targets for e.g. angiogenesis inhibitors or cell proliferation inhibitors and validation of their biological relevancy based on chemical genetics provide in addition new insight for the biological role of certain targets as well valuable information for the development of new active compounds.
A forward chemical genetic screen has been applied to screen for compounds that are capable of inhibiting proliferation of cancer cells. This approach has led to a novel series of compounds useful for the treatment and/or prevention of proliferative diseases.