Background

In life sciences research, chemical compounds that interact with biomolecules are critical for understanding biological processes and for developing biochemical reagents and/or therapeutic drugs. 

• Exposing a cell to an inhibitor for an enzyme can block the biological pathway and provide a clue to the enzyme's importance in the cell's function.
• Using fluorescence microscopy, a flurescently-tagged ligand for an intracellular receptor can indicate which portion of the cell the protein resides.
• Performing biological activity assays with various structural analogs for an enzyme's normal substrate can identify a new strong-binding reagant to serve as either an inhibitor or probe. 
• Particularly strong enzyme inhibitors that also have bioavailable properties may be able to serve as targeted therapeutic medications in disorders caused by the enzyme's dysfunction.

PubChem contains not only chemical information, but biological assay studies with data as well. In 2004, the PubChem project was originally developed to serve as a data warehouse for the NIH Molecular Libraries Program. This initiative was created for large-scale screening of small molecules that could be optimized as chemical probes to study the functions of genes, cells, and biochemical pathways in health and disease. It was also intended to help validate new drug targets, which could then move into the drug-development pipeline. 

The PubChem BioAssay database was created to house information about in vivo, in vitro and biochemical bioactivity experiments measuring the impact of small-molecules and inhibitory-RNAs (RNAi) along with the screening data from submitting organizations.  BioAssay contains a collection of bioactivity and toxicity data that has greatly supported research in fields such as medicinal chemistry, drug discovery, pharmaceutical genomics and informatics research. 

Searching for bioassay-related information in PubChem

While you can certainly type in key words such as gene symbols or experimental method types into the search box to find related bioassay information, using standard Entrez Search Syntax allows you to really customize and retrieve more specifically what you are looking for using Indexed Filters and Fields.  

Example Search Strategies:

Finding a potential inhibitor- KIT Example

Proto-oncogenes are genes that code for proteins that help regulate cell growth and differentiation. The human kit protooncogene encodes a receptor tyrosine kinase which is a potentially important drug target because atypical kit protooncogene's gene expression leads to diseases like gastrointestinal tumors, mast cell disease, and leukemia.  

We'd like to:

• Learn more about the kit protooncogene - in NCBI's Gene database, but also in PubChem's Gene pages
• Find chemicals that were tested for activity against this gene product
• Narrow the list down to one that might be a good inhibitor to use for our own studies
• Identify one with chemical vendor information

To learn more about the human kit protooncogene:

To find compounds tested against the human c-kit gene product:

Select a compound to learn more about!

Find the PubChem Compound record for the proposed inhibitor and link to a vendor:

Congratulations on finding a reagent. Contact the vendor and good luck with your  experiments!

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Take-away Message

• You can leverage fundamental search strategies we've learned and your knowledge of PubChem BioAssay to gain exhaustive information about your target protein or gene, including information on potential inhibitors!
• PubChem Text Search, PubChem Gene pages,  PubChem BioAssay, and PubChem Compound were key resources for this exercise. Review PubChem sponsored documentation for more information