A new method of drug development which expedites the lengthy process of scanning thousands of possible combinations, could lower drug prices substantially
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."
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