Datamining finds new target for diabetes treatment
22 February 2009
A team of researchers from Oxford and Southampton Universities have
identified a new molecular player in insulin secretion
process by mining a free database of 5 million drug compounds. This finding
could spark a completely new class of drugs to treat type 2 diabetes.
In work published today in Nature Chemical Biology  and
funded by the UK Biotechnology and Biological Sciences Research Council,
the researchers explain how they have exploited new technology to
create a cheap and efficient method of drug discovery that will allow
small academic labs to search a large database of drugs to find
treatments for diabetes and many other diseases.
They have used this new method to identify a small molecule which
they are using to understand how insulin is secreted in response to
increases in blood sugar.
Lead researcher Dr Grant Churchill said: "A lot of diseases are
caused by problems with important proteins within cells. We need to find
small molecules that change the function of these proteins both to
discover how they work and in addition because these small molecules may
also work as treatments for disease.
"The approach we have developed allows us to do this much more
quickly and cheaply than many of the current methods. Ultimately this
will speed up the process of getting better treatments into the clinic
Starting with a natural chemical and systematically modifying its
chemical structure is a proven technique and common drugs such as
beta-blockers and anti-histamines were discovered this way. However,
these discoveries involved lengthy chemical syntheses starting with the
natural chemical (adrenalin and histamine respectively).
"Our method also begins with the natural chemical but rather than
modifying it with a time-consuming and expensive chemical syntheses
conducted by a team of chemists, ours uses computers to identify
corresponding small molecules for research and medicine.
"The major difference is that we have linked the computational
methods commonly used by pharmaceutical companies to a freely available
database of 5 million existing compounds — the ZINC database . This
means we cut out a hugely time-consuming and financially intensive part
of the process, which is difficult for small academic labs to do,"
The research team has tested their method by successfully identifying
a small molecule called Ned-19. This molecule was found after
information about the natural chemical NAADP was entered into the
computer system and cross referenced with the ZINC database.
In collaboration with scientists at the University of Southampton,
led by A Ganesan, Ned-19 was prepared on a larger scale and separated.
Further experiments were carried out with these compounds to confirm the
activity of Ned-19. Using Ned-19 in experiments they have discovered
that NAADP plays a crucial role in insulin secretion and therefore
represents a brand new target for diabetes drugs.
Churchill continued: "Unfortunately, asking someone to take Ned-19
would actually give them diabetes! But now that we know how important
NAADP is we can start to look for drugs that work with NAADP to increase
insulin secretion rather than decrease it. In fact, we have colleagues
who are already working on this using our tool."
Professor Douglas Kell, BBSRC Chief Executive said: "This is great
news for our community of researchers and will provide a powerful tool
for research in the future. This discovery about insulin secretion shows
how important it is to have centrally held data repositories that are
free to access. Such sharing of data and information can have really
significant impact, right across the board."
1. Nature Chemical Biology. doi: 10.1038/nchembio.150. The
journal can be found at:
2. The ZINC database is provided by the Shoichet Laboratory in the
Department of Pharmaceutical Chemistry at the University of California,
San Francisco (UCSF). ZINC is at
3. See also a blog on drug discovery by BBSRC Chief Executive, Professor
Douglas Kell (opens in new window) at:
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