Reverse chemical genetics approach

Scheme 7.1-2 Flow scheme for a reverse chemical genetics approach.

Identification and selection of disease-specific targets is one of the most important steps toward personalized medicine. The simultaneous identification of disease-specific protein targets and their small molecule binding partners, suitable as drug candidates after validation with a cell-based approach (a reverse chemical genetics approach), could radically reduce the timeline and costs of drug discovery and develop-menf. Diverse small molecule microarrays were applied to identify such profeins directly from cancer cell lysates/fractions in comparison with... 

Reverse chemical genetics approaches start with a known gene or protein target of interest of which it is known that alteration of its function causes a certain phenotype. Subsequently, a compound collection is screened to identify small molecules that bind the target and alter its function in the desired way. Hence, the reverse chemical genetics workflow is from gene to compounds. Usually, in vitro experiments are carried out ahead of in vivo experiments. 

Target-based screening, also called the reversed chemical genetics approach, aims to identify small-molecule modulators for a known protein of interest. The identified compounds are then employed to study protein function in cellulo or in vivo. 

Discovery of Small Molecule Probes Using a Reverse Chemical Genetic Approach... 

The reverse chemical genetic approach begins the discovery of a small molecule modulator of a specific target protein. The small molecule is usually identified... 

General Reverse Chemical Genetic Approaches for Targeting Specific Members of Families of Macromolecules... 

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