KU grant background information: Molecular libraries research

Overview
Pharmaceutical scientists have to test thousands of compounds to find the few that might be turned into a drug. Such testing is called "high throughput screening" in the pharmaceutical industry and is used in virtually every kind of drug discovery research, whether its goal is to find a new agent to treat heart disease, Parkinson's disease or mental illness.

To do the screening, a researcher first must have tens of thousands of compounds on hand in what are called "libraries." The new Chemical Methodology and Library Development Center of Excellence at the University of Kansas is devoted to finding out what makes libraries better. The KU team will apply years of experience in learning about how drugs work on a molecular level to building libraries that have an optimal chance of containing that magical molecule that makes it, as a drug, to the bedside.

Very few molecules will qualify as drugs
All drugs -- whether they treat cancer or Alzheimer's disease or a mild infection -- are made from molecules.

But drug molecules must have special properties. A perfect drug will not just treat a patient's disease or condition. It also won't be toxic to the patient or produce side effects. And it will be suitable for administration in pill form.

This is a tall order. Finding the right molecule requires knowledge, intuition, hard work and luck. Nowadays, it is common for medicinal chemists to make about 10,000 different molecules before a single drug reaches the bedside.

Making more molecules -- faster -- increases the chance of drug discovery
A top medicinal chemist preparing one molecule at a time might be able to make 100 molecules a year. Obviously, that kind of pace represents a major clog in the "pipeline" of drug development.

A relatively new technique called combinatorial chemistry is quickening the pace of molecule-making and raising the odds of drug discovery. Instead of making one molecule at a time, the combinatorial chemist makes collections of molecules -- 30, 96, 1,000 -- sometimes even a million at a time.

Vast numbers of molecules may be stored in libraries
These collections are called "libraries" because they contain a tremendous amount of chemical information that can be mined by biologists, chemists and computer scientists. Libraries of molecules are just like libraries of books: One can go to either kind of library again and again to solve different kinds of problems.

The challenge in making and keeping track of these molecules requires both new chemical techniques and a new mindset in the medicinal chemist. One of the benefits of this approach is that the chemist makes new compounds in relatively small quantities -- that is, in environmentally friendly amounts.

The KU center will help accelerate the production of molecules ready for testing
The KU Chemical Methodology and Library Design Center of Excellence brings together more than a dozen researchers at KU, the KU Medical Center in Kansas City, Kan., and Iowa State University in Ames. They will develop new techniques for doing combinatorial chemistry, the foundation for assembling the libraries.

KU brings to the center long-standing expertise in medicinal chemistry and organic chemistry. Researchers in these disciplines will collaborate with others in pharmacology, pharmaceutical development and chemical analysis as the KU-CMLD seeks to design libraries of molecules. Years of experience designing drugs the old-fashioned way will be fused with the promise of new technology. The resulting libraries will be made available to the biomedical research community worldwide, as well as to local scientists seeking to invent new drugs or understand the biological bases of human health.

Kansas City life sciences
"The KU Combinatorial Methodology and Library Development Center adds significantly to the life sciences initiative in the greater Kansas City area," said William B. Neaves, president and CEO of the Stowers Institute for Medical Research in Kansas City, Mo. "Basic research at the Stowers Institute and other KCALSI (Kansas City Area Life Sciences Institute) institutions reveals genes and proteins that govern fundamental processes in living cells, and these discoveries become targets for new drug development. Jeff Aube and his colleagues in the center will greatly expand the inventory of small molecules with the potential to influence these targets therapeutically."