Successful application of software from BioSolveIT

In the undeveloped world, over 350 million people are at risk from neglected diseases. Existing drugs to treat these diseases are often expensive, difficult to administer, unsafe and increasingly ineffective due to development of resistance by the parasites that underpin these conditions. To this end, two years ago the Wellcome Trust awarded £8.1 million over 5 years to the University of Dundee to help discover new drugs to treat some of the world's most neglected tropical diseases.

The goal of this initiative is to translate basic research discoveries into candidate drugs ready for clinical trials. The diseases, which include African sleeping sickness, Chagas' disease and Leishmaniasis, are among the most neglected in the world, affecting millions of the world's poorest people and attracting little or no interest from pharmaceutical companies.

In the most progressed project to date a compound series has been discovered that shows nanomolar affinity against the target and good oral efficacy in the disease model. In the absence of a crystal structure of the target the application of FlexS was crucial to help to derive a pharmacophore model from the initial hits in order to guide hit validation and optimization. While further optimization is still ongoing, the Feature Trees program is currently used to support the quest for a backup series.

The computational chemists in the team were generally impressed how easy and quick it was to learn how to use the BioSolveIT software tools and were very pleased that they did not come across any bugs. We consider these tools a vital ingredient to our scientific work and look forward to further broaden their application in the future.

Dr. Ruth Brenk
Biological Chemistry and Drug Discovery
College of Life Sciences
University of Dundee
Dow St., Dundee, DD1 5EH, U.K.