Taking a short cut

30/05/1996
Down To Earth

Taking a short cut DRUG development may not take as long as it once did. A new method of 'combinatorial chemistry' is being tested at a laboratory of Pharmacopeia Inc in Princeton, New Jersey, us. To rapidly screen scores of chemicals against diseases, combinatorial chemistry employs computers, robots and biotechnology research information to come up with a new drug in shorter time span.

Pharmacopeia has been entrusted the job by pharmaceutical giant Schering-Plough Corp, us, which, apart from identifying the compounds, also hopes that this new testing process will cut down drug-finding costs substantially and could revolutionise pharmaceutical development.

Conservative drug-making depends mainly on probability and luck. The laboratory has to identify compounds most effective against certain diseases and choose from the thousands of compounds in their chemical library. Out of 10,000 compounds screenel, only a 100 may show enough promise to warrant further investigation for developing a new drug. And from these, only 10 might be used in human trials and finally one will be put on the market. This method of drug development on an average takes 12 years and some us $350 million from conception to the delivery stage.

Scientists at Pharmacopeia take hundreds of simple chemicals and hook them onto inert plastic beads, which act as a support to hold the molecule in place as other chemicals are added onto it. These beads are then strung together in specific recorded combinations which are then given a particular 'chemical identity'.

Robots then take these chemical combinations and pour them into a dozen or so one-inch hollow wells on plastic trays. These wells contain a liquid in combination with a protein or any other agent causing a specific disease. 'The trays are then passed through scanners which signal the success of the combinations through increased radioactivity or uv waves. One out of 100,000 chemical combinations may require further investigation. Once an active well is identified, each of the strings are then tested to find which one reached the agent and brought about the reaction. The scientists then start the screening process all over again by testing numerous chemical variations to identify the best combination.

According to Edward Hurwitz, senior biotechnology analyst for the investment banking firm of Robertson Stephen and Company in San Francisco, us, "CombinatoTial chemistry is a fundamental paradigm shift in drug development. You are now screening millions of compounds in months or weeks, whereas earlier it used to take years to screen thousands."

Combinatorial chemistry has been doing the rounds for the last eight-10 years, but it was only in the last three years that it got noticed. It is still in its infancy as it has yet to come out with its first major drug. The pharmaceutical companies are, however, in for a booming business by associating combinatorial chemistry with information available in the field of genetics and biological sciences.

Combinatorial chemistry will be used to screen tens of thousands of natural and synthetic compounds stored by drug companies like Merck and Pfizer in their chemical libraries. Many of these compounds have not been screened for drug development due to lack of a quick screening method. Through conventional methods, a chemist can create about 50 new compounds a year at a cost of us $5,000- 7,000 each. Using combinatorial chemistry, Pharmacopeia can increase the number to 100,000 new compounds annually per chemist, costing not more than a few dollars a compound.

Pharrftacopeia's laboratory contains small molecules', which are simple chemicals and can withstand the human digestive system without being destroyed. These can be developed as oral drugs.

A biotechnology analyst at Cowen and Company in New York, David Stone opines that drug companies can no longer profit if they concentrate on making minor changes in existing drugs. "The place to be in is breakthrough drugs, a drug that works by a new mechanism," he says, adding that "Pharmacopeia is the fast-food of drug screening."

Tags:

India Environment Portal Knowledge for change

Browse by subjects