www.Find-a-Drug.org   9 July 2003 Issue 4
 

 Cancer Growth Inhibitors Found

At the end of June, Find-a-Drug was pleased to announce that the preliminary results of its Cancer Internet project had exceeded all expectations. As a result of the generous contributions of PC time by members, Find-a-Drug has been able to evaluate the potential of more than 0.5 billion molecules and produce a set of molecules that are predicted to inhibit the growth of various types of cancer cell. Scientists at the US National Cancer Institute have tested the abilities of a small number of molecules from the set as part of their Developmental Therapeutics Program.

"We had expected that only 2-3% of the molecules predicted to inhibit cancer cell growth would be observed to do so in the laboratory" commented Keith Davies, Scientific Director of Find-a-Drug. "In this study, 7 of the 39 molecules tested showed the desired anti-cancer properties".

These results relate to two proteins: RAS, which has been described by David Kerr, Professor of Oncology at of Oxford University as the "single access gate" for signalling cell development; and VEGFr which plays a key-role in the development of new blood vessels. Previous attempts to find RAS inhibitors have been less successful, but there are some VEGFr inhibitors in clinical trials. VEGFr is a very attractive protein to target because inhibiting the development of new blood vessels would be a valuable treatment for most solid tumours including breast, colon and renal cancers. VEGFr inhibitors may also be a viable alternative to chemotherapy following surgery with fewer side-effects.

Find-a-Drug hopes to test more molecules in the laboratory later this year before making any decisions about which molecules are worthy of further research. We expect that the percentage of tested molecules which show activity will fall below 10% when the results for other molecules and proteins are analysed. Alternative protein targets will also be evaluated to increase the number of molecules which are predicted to have anti-cancer properties. It is hoped that choosing from a larger number of molecules will help to avoid drug failures during clinical trials. Further information will be posted on the web-site.

SARS

The Respiratory Disease project started in May, shortly after the previous newsletter was released. The first targets were related to Severe Acute Respiratory Syndrome (SARS), and at the time of writing both are nearing completion. Subsequent targets may include Tuberculosis (TB) and Chronic Bronchitis which are responsible for the deaths of many people worldwide.

The 3-D structure of the SARS virus proteinase was determined by Professor Hilgenfeld at the University of Lübeck who has kindly made it available to Find-a-Drug. As part of the collaboration with Professor Hilgenfeld, the hits from this work will be made available to his group and they will attempt to confirm the binding to the protein site.

 

 HIV project

The long awaited start of the HIV project came earlier this month. The first target gp120 plays a key role enabling the entry of HIV into human cells, and a molecule which inhibits this process would be a novel drug. The site we are examining in gp120 is largely conserved across HIV-1 mutants, thereby reducing the scope for drug resistance!

The region of the world most affected by AIDS is sub-Saharan Africa. Over 23 million adults and children in the region are currently living with HIV/AIDS and more than 13 million have died, accounting for over 80% of the world's deaths due to AIDS. In Africa alone 10,000 people become infected each day, according to UNAIDS. For many of these individuals the prospects are bleak: the life-time costs of the current generation of drugs are economically crippling and the medical facilities are limited, with the consequence that most sufferers face a miserable life and early death. New mutations of HIV threaten the effectiveness of current antiretroviral drugs and are challenging scientists to find better drugs.

"I am excited by this approach to identify potential new drugs", comments Dr Ian Gilbert of the Welsh School of Pharmacy at Cardiff University, who is collaborating with Find-a-Drug. "The scale of this project might allow us to find a molecule which is effective against the human immunodeficiency virus which causes AIDS."

Certificates

Messages posted in our forum indicate that there are a variety of reasons why people participate in Distributed Computing projects. Knowing the suffering that a disease can cause is often a sufficient reason, but participation can be made more fun by joining teams. This is especially the case for more competitive members who keep track of their relative contributions.

We have recently added the capability to create and print certificates to acknowledge the contributions made by members as they pass certain milestones in terms of the numbers of molecules processed or points awarded. In addition, special certificates are issued when preliminary results indicate that a member has found a molecule which exhibits the desired biological activity. We are grateful for the assistance provided by Japonicus in drafting the original PHP script to create the certificates.


Find-a-Drug is a tradename of Treweren Consultants Ltd Copyright © Treweren Consultants Ltd 2003