Chemical-genetic approaches are based on measuring the cellular outcome of combining genetic and chemical perturbations in large-numbers in tandem. In these approaches, Creative Biolabs evaluates the biocompatibility of different genes by contacting different chemicals. Our state-of-the-art technology enables chemical genetics to be applied to a wide range of physical samples with great efficiency, helping customers promote their drug development projects.

Chemical Genetics in Drug Discovery

Chemical genetics generally refers to a systematic assessment of the effects of genetic variation on drug activity. Chemical genetics was first established in the field of microbiology and is now increasingly used in human cell lines. As more and more experimental tools are developed, our chemical genetics related services can assist in the development of drugs in a number of ways, including identification of Mode-of-Action (MoA), mapping of uptake and efflux routes, revealing of resistance mechanisms and understanding of interactions with other drugs. Similarly, chemical genetics can also be analyzed in array libraries using experimental automation and image processing software. Hundreds of thousands of mutants can be analyzed in the same plate. In the array form, the effects of drugs can be evaluated by other macroscopic phenotypes other than growth, such as biofilm formation, spore formation, DNA uptake, or cell lysis. Although microbial chemical genetic screening focuses on measuring the overall phenotype, with the recent developments in high-throughput microscopy, it is also possible to quantify single-cell phenotypes and population behavior in mutant libraries. In this case, the cellular markers and classifiers of the drug response can further understand the biological activity of the drug in the cell.

Conventional target-based drug discovery approach versus chemical genetics drug discovery approach. Fig.1 Conventional target-based drug discovery approach versus chemical genetics drug discovery approach.

Targeting Mapping by Chemical Genetics

Creative Biolabs uses chemical genetics to identify and characterize potential targets in natural compounds in two ways.

  • Gene Expression Libraries. We use libraries in which the levels of essential genes, the usual target of drugs, can be modulated. When the target gene is down-regulated, the cell becomes more sensitive to the drug, and overexpression of the target gene has the opposite effect. Currently, knockdown and overexpression methods are now beginning to be used by us to identify drug targets in human cell lines.
  • Drug Signatures Comparation. A second way to infer the drug target from chemical genetics data is by comparing drug signatures. We can identify repeated chemical genome characteristics that reflect the general drug MoA and predict drug interactions.

If you have any questions about our drug discovery service, you can contact us by email or send us an inquiry to find a complete solution.

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