Database Evaluates Molecules for Carcinogens, Toxins

Contact: Toni Searle, [email protected]

CLEVELAND -- Thousands of animals used in research may have a new lease on life, thanks to a software program developed by a Case Western Reserve University chemist.

The program, MCASE (Multi-Computer Automated Structure Evaluation), is a database of known toxic and carcinogenic chemical molecules.

The creation of Gilles Klopman, CWRU's Charles F. Mabery Professor of Research in Chemistry, MCASE can help chemists determine within minutes whether a new chemical presents a liability for cancer, birth defects, side effects, or environmental hazards. (Klopman's Web page is at http://chemwww.cwru.edu/Faculty/klopman.html.)

MCASE organizes chemical information into categories, Klopman said. Chemists still have to create the chemical molecules, but can submit chemical structures to the program, which will evaluate the potential toxicity.

MCASE is licensed through Multicase Inc. of Beachwood. The company entered a Cooperative Research and Development Agreement earlier this year to allow the Food and Drug Administration's Center for Drug Evaluation and Research to use MCASE.

The FDA will input information from its files on known toxins and make this information available to drug manufacturers through the software program.

"The results (of the agreement) will give toxicologists an unparalleled decision support tool to aid and facilitate product development and regulatory review processes," Klopman said.

Klopman formed Multicase with Herbert S. Rosenkranz, an adjunct professor of the School of Medicine and the professor and chairman of the University of Pittsburgh's Department of Environmental Health.

During a lecture in the 1980s, Rosenkranz challenged the audience to develop the tools that would give chemists a head start on designing environmentally friendly products.

A solution came to Klopman during an airplane ride from Texas to Cleveland in 1981. Since that original software package, CASE, Klopman created other software packages on chemical substances and their reactions -- META, CASETOX, ToxAlert, and MCASE -- during air flights.

Klopman had lent MCASE to the FDA for a six-month trial period two years ago as the organization began to look for ways to computerize its information.

The FDA has already entered information about carcinogens and birth defects. It provides information gathered from public and non-proprietary information in its files. As new information is entered, MCASE licensees will receive ongoing updates.

MCASE can help save billions of dollars in research costs. "It takes approximately $2 million to test each chemical on rats," Klopman said.

It also can help more drugs reach the public faster, as drug designers can target chemical substances with promising outcomes or know the potential liabilities of others.

Certain drugs change their chemical structures over time, he noted. MCASE can assist in analyzing drugs' degradation products.

It won't eliminate all animal testing, said Klopman, but it will prevent drug companies from testing chemical compounds which have been predicted to be harmful.

About 99.9 percent of the chemicals that go into drugs, pesticides, cosmetics, perfumes, and other products used by humans fail in laboratory tests, Klopman added. That can mean hundreds of rodent lives per test.

For guinea pigs of all kinds, it's a new day in research -- one that animal rights advocates will applaud, said Klopman.

-CWRU-