Collaborative Drug Discovery, Inc. (CDD, Inc.) and St. Jude Children’s Research Hospital have joined together for a project aimed at speeding the development of new drugs to overcome resistant strains of malaria.
The collaboration combines the malaria drug data and informatics technology of CDD with the drug discovery expertise of the St. Jude Department of Chemical Biology and Therapeutics. Informatics is the use of computer hardware and software to extract and manage knowledge from large databases.
“CDD’s databases will probably help us reduce the number of potential molecules we’ll need to analyze from tens of millions down to hundreds of thousands,” said Kip Guy, Ph.D., chair of the St. Jude Department of Chemical Biology and Therapeutics. “Our own screening capability will significantly reduce that to a much smaller number of promising compounds.
This will be a widely used database. We are already making the data freely available through CDD so that other researchers can use different analytical strategies to identify potential new anti-malarial drugs.”
The collaboration is designed to help scientists quickly screen millions of chemicals, based on their structure and their chemical and biological properties, to find those that are most likely to make effective anti-malaria drugs. The key to this quest to find the drug “needle in the haystack” is the enormous two-volume collection of data from studies on malarial drugs published by the U.S. Army in 1946.
This 61-year-old publication, “A Survey of Malaria Drugs,” was originally edited by Frederick Y. Wiselogle and had contributions from a number of leading researchers of the time. The two-volume set was designed to help researchers develop effective anti-malarial drugs; and to serve as a model for how scientists could develop drugs for other infections, according to the authors of that publication. The collection presents the structures of many compounds and the results of studies on their biochemical activity in animals, data on how they work in the body, how long they last, and other pharmacological data, in addition to their level of toxicity. The results of the animal studies represent one of the largest sets of published data on the structure-activity relationship (SAR) of molecules against a single disease, Guy said. SAR refers to the link between a molecule’s specific structure and the biological effect it has because of that structure.
CDD scanned the information from the original publication into a computer database and organized it into a format that can be read, searched and shared. This more convenient format will enable St. Jude scientists to use the information to develop models of new anti-malaria drugs and predict their efficacy, toxicity, and how the body will respond to them.
Based on such models, St. Jude researchers are conducting a comprehensive analysis of “relevant chemical space” of these molecules, something that has never before been done for malarial drug research, Guy said. Relevant chemical space refers to the study of individual families of molecules whose members all share a similar structure that holds promise for a specific therapeutic use. Concentrating on only certain families of molecules likely to have the desired effect saves time and speeds the discovery of the few molecules most likely to have all the characteristics needed for an effective anti-malaria drug, he said.
The anti-malarial drug study is the first of several planned by CDD to help the research community discover drugs for orphan infectious diseases—disorders for which there is little commercial interest in developing drugs. Future CDD communities are planned in other more commercial areas, such as cancer research and selected gene families.
To access this historical set of Malaria Animal SAR data for the first time, either visit https://app.collaborativedrug.com/register or e-mail email@example.com for the username and password to the open data sets.
CDD is the world’s first platform for selectively sharing collaborative drug discovery data. Scientists working with the CDD community platform can pool their research in order to more effectively develop new drug candidates for commercial and humanitarian markets. Conceived in 2003, and formally launched in 2004,
Collaborative Drug Discovery (CDD) has been serving the collaborative data needs of researchers for years. The CDD global community includes hundreds of scientists from leading research foundations, academia and industry. A subset of the data is available openly to the public at no cost.
St. Jude Children’s Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is
financially supported by ALSAC, its fundraising organization. For more information, please visit www.stjude.org.