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Chemical Genomics

What chemicals can be used to study cell function at the genomic level?
Why do we need libraries of these chemicals?
What advances make it possible to build public chemical libraries?
How many chemical compounds will be in public sector libraries?

What chemicals can be used to study cell function at the genomic level?

A class of organic chemicals, commonly referred to as "small molecules," has proven to be extremely important to researchers exploring the functions of the cell at the genome level. Such molecules are also valuable for treating everything from headaches to cancer. In fact, most medicines, from aspirin to antihistamines, are small molecule compounds.

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Why do we need libraries of these chemicals?

It remains difficult to predict which small molecule compounds will be most effective in a given situation. Researchers can maximize the likelihood of a successful match between a chemical compound, its usefulness as a research tool or its desired therapeutic effect by systematically screening libraries containing thousands of small molecules.

As part of the National Institutes of Health (NIH) Roadmap for Biomedical Research, the National Human Genome Research Institute (NHGRI) will lead an effort to offer public sector biomedical researchers access to libraries of small organic molecules that can be used as chemical probes to study cellular pathways in greater depth. This initiative will provide new ways to explore the functions of major components of the cell in health and disease. In addition, it is hoped these public chemical libraries will speed development of new drugs and agents to definitively detect and treat disease by providing early stage compounds that encompass a broad range of novel targets and activities. These compounds will help validate new targets for drug therapy more rapidly, and will enable other researchers in the public and private sectors to take these targets and move them through the drug-development pipeline.

The development of such libraries will also enhance the discovery of small molecules for molecular imaging - the imaging of molecules or molecular events in biologic systems that span the scale from single cells to whole organisms. Ultimately, it is hoped that this effort will enable doctors to obtain personalized profiles of cell and tissue function for each patient, leading to more individualized approaches to diagnosis and treatment.

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What advances make it possible to build public chemical libraries?

Three key technological advances drive NIH's effort to build small molecule libraries. First, the successful completion of the Human Genome Project, which was the effort to sequence all 3 billion base pairs in the human genetic blueprint, has provided an enormous cache of biological information and identified a wealth of potential new drug targets. Second, developments in combinatorial chemistry have given academic researchers access to compounds previously available only to researchers in the private sector within pharmaceutical and biotechnology companies. Third, advances in robotic technology and informatics now allow investigators to screen hundreds of thousands of compounds in a single day, orders of magnitude greater than was possible a decade ago.

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How many chemical compounds will be in public sector libraries?

To provide maximum benefits, the library of small molecules must contain a sufficient number of compounds to be screened for a large number of possible new activities and applications. To build such a library, a network of national centers will initially establish a collection of 500,000 chemically diverse small molecules, of both known and unknown activities. Over time, this collection will be expanded and modified to provide a working set of compounds that will target larger domains of "biological space," the total set of biomolecular surface domains capable of interacting with a small molecule.

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Last Reviewed: July 23, 2008




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See Also:

Chemistry and Biology: Partners in Decoding the Genome
A symposium on
chemical genomics held March 15-16, 2004

On Other Sites
NIH Chemical
Genomics Center
(NCGC)

NIH Roadmap
for Medical Research




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