KU receives $9.5M to assemble molecular 'libraries' used in new drug research

LAWRENCE -- The National Institutes of Health has awarded a $9.57 million grant to the University of Kansas to do research that will help assemble extensive "libraries" of molecules that scientists use to develop new drugs.

The grant will help establish a KU Combinatorial Methodology and Library Development Center of Excellence, or KU-CMLD, as the umbrella organization for the research. Fifteen investigators will take part in the research -- 12 at KU, one at the University of Missouri at Kansas City, one at Iowa State University at Ames, and one at Deciphera Inc., a Lawrence-based company.

KU and Harvard University are the only two universities in the nation to receive CMLD awards this year. The KU and Harvard centers join Boston University and the University of Pittsburgh as the third and fourth NIH-funded programs devoted to the development of libraries of molecules.

"KU brings a unique and valuable medicinal chemistry perspective to this program," said John Schwab, who directs the CMLD program for the National Institute of General Medical Sciences, one of 20 NIH agencies. "This will be the only one of our four CMLD centers with a historical commitment to the development of therapeutically active molecules."

Jeffrey Aube, a KU professor of medicinal chemistry and project leader for the effort, said the investigators would work on methods for designing the chemical backbones that are the basis for molecules contained in a given molecular library.

A well-made library of molecules can contain anywhere from a few dozen compounds to millions, Aube said. But only a tiny fraction of these have potential as drugs. Before the days of molecular libraries, a medicinal chemist might come up with 100 molecules a year with drug potential -- producing one at a time. Today, said Aube, a technique called combinatorial chemistry is quickening the pace of molecule-building. "Instead of making one at a time, the combinatorial chemist makes collections of molecules -- 30, 96, 1,000, even a million -- at a time."

Identifying a molecule with drug potential amid all the candidates is like finding a needle in a haystack, Aube said. "It's common for a medicinal chemist to synthesize about 10,000 different molecules before a single drug reaches the bedside."

This means that the bigger the library of molecules, the greater the chance of finding some with drug potential. The work at the KU center will help expand the libraries by hastening the discovery of new and novel molecules, Aube said.

The new center will complement the work being done by many of the facilities in the Kansas City area that are involved in medical research. Bill Duncan, president of the Kansas City Area Life Sciences Institute (KCALSI), said, "The NIH award to establish the KU-CMLD is yet another step toward recognizing technical excellence in our regional universities. It will clearly have a significant impact on the overall life sciences initiative in the region."

"Basic research at the Stowers Institute and other KCALSI institutions reveals genes and proteins that govern fundamental processes in living cells, and these discoveries become targets for new drug development," said William B. Neaves, president and CEO of the Stowers Institute for Medical Research in Kansas City, Mo. "Aube and his colleagues in the center will greatly expand the inventory of small molecules with the potential to influence these targets therapeutically."

An important mission of the new center is to make newly developed methods and resources available to other scientists. For example, at KU's Center for Cancer Experimental Therapeutics, led by Gunda Georg, researchers will use the molecules developed by the CMLD to find new drugs to fight cancer. "All the compounds they find ¹ will come to us," said Georg. "This effort will allow us to find new pharmacological tools and potentially new drugs."

The awards to KU and Harvard are part of an NIH initiative called Roadmap for Medical Research announced Sept. 30. The initiative is aimed at speeding the progress of research discoveries from lab bench to bedside.

WEB RESOURCES

KU Center for Research: www.research.ku.edu/kucr/
KU Department of Medicinal Chemistry: www.medchem.ku.edu/
KU Professor Jeff Aube: www.medchem.ku.edu/Faculty/aube.htm
NIH Molecular Library: nihroadmap.nih.gov/molecularlibraries/index.asp
NIH Roadmap for Medical Research: nihroadmap.nih.gov/