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The
article below recently appeared in July 2006
issue of Chemistry World - http://www.rsc.org/chemistryworld/News/2006/June/03070601.asp
The Johns Hopkins Clinical Compound Library (JHCCL)
is the largest readily accessible collection of
approved drugs available for this kind of
screening survey, said David Sullivan of the
Johns Hopkins Bloomberg School of Public Health,
Baltimore, Maryland, US, part of the project
team.
Astemizole is proof that screening existing
drugs for previously unknown activities could
help speed up the expensive and time-consuming
process of drug development, said Sullivan. He
and his colleagues, including Curtis Chong and
Jun Liu, have spent about four years collating
the library, which cost roughly $500 000 (£275
000) and was largely funded by the Johns Hopkins
Malaria Research Institute.
The antihistamine astemizole
could help in fight against malaria
The JHCCL contains 1937 drugs that have been
approved by the US Food and Drug Administration
(FDA), along with 750 drugs that have either
been approved for use in other countries or are
undergoing Phase II clinical trials, making it
at least twice as big as other such libraries.
Surprise activity
The JHCCL’s drug stocks are mostly stored
in solution, and small portions must be
transferred into trays of tiny containers for
automated testing. ‘But you could screen the
whole library in a week, maybe less, depending
on your assay,’ said Sullivan.
An initial screen of the drugs’ activities
highlighted 189 existing drugs that could
inhibit the growth of Plasmodium falciparum, one
of the parasites that causes malaria. The team
shortened the list by ignoring known
antimalarials and cytotoxic drugs, and
identified astemizole as a promising
antimalarial drug after testing it in mice
infected with malaria parasites. ‘It was a
surprise to find this activity,’ said
Sullivan.
Astemizole was first marketed as an
antihistamine in 1983 under the brand name
Hismanal, and although it has been withdrawn in
the USand Europesince alternative drugs with
fewer side effects became available, it is still
sold in generic form in more than 30 countries.
It is readily available in Cambodia, Thailandand
Vietnam, where malaria is endemic. Previous
research has found that some antihistamines can
boost the effects of antimalarial drugs when
used in combination.
Astemizole attacks the parasite in a
different way from the common antimalarial agent
chloroquine, which means that it may be
effective against resistant strains of malaria
parasite, said Sullivan: ‘It’s a proof of
principle for the library screening process, but
we’re optimistic that it might also be a
viable combination drug.’
The general principle of trawling through
approved drugs for additional benefits is a good
idea, said Peter Winstanley, a malaria
researcher at the University of Liverpool, UK.
‘It means that a lot of the preliminary work
has been done, and that does make it cheaper,’
he said. But he cautions that even if drugs are
already approved, they still have to go through
fresh clinical trials for additional diseases
before they are used, a process that could take
five years or more.
Summer special
Sullivan admits that pharmaceutical companies
are likely to have larger in-house libraries,
but points out that those are not always easily
accessed by academic researchers. ‘And
hospitals might have a larger number of drugs
collected on their shelves, but that’s not
suitable for rapid screening purposes,’ said
Sullivan.
So far, the library has only been used by
Sullivan’s team and a handful of other Johns
Hopkins’ scientists. ‘We’re not quite
ready to have people call up and ask for the
library,’ said Sullivan. But he expects that
by the end of the summer they should be able to
supply other scientists with small samples of
all the library’s drugs, at the relatively low
cost of a few thousand dollars.
Sullivan hopes that the JHCCL project will
eventually collaborate with other partners to
include every available drug ever used in
medicine, which would swell the library to about
11 000 compounds.
Mark Peplow
To read this article go to - http://www.rsc.org/chemistryworld/News/2006/June/03070601.asp
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