The SBS Symposium on Biomolecular Screening, held through Oct 18 – 19, 2010 in Research Triangle Park, Durham, NC brought together leading scientists in academia, government and industry to discuss screening applications in drug discovery. Chris Austin opened the symposium with a keynote presentation on the screening applications at the NIH Chemical Genomics Center (NCGC) that focus on small molecule and siRNA screens. NCGC takes a collaborative approach to screening where they provide the screening library and automation and their collaborators provide the drug target and its biological hypothesis for disease involvement. The goal of the screening campaign is not typically to provide leads for optimization, but to find chemical probes for further target validation relative to the disease state.
Bob Hertzberg represented Pharma in the opening session and gave an interesting look at small molecule drug discovery at GSK over the last decade. This was done by providing an overview of key drug discovery initiatives over that period. It began with scaling up HTS infrastructure, following up with the industrialization of the HTS process and driving efficiency, then focusing on solving drug attrition when the leads coming out of the HTS campaigns failed, and ending with the current initiatives focusing on flexibility and return on investment. An interesting point was made concerning drug attrition where the practices of driving small molecule potency to nM – pM levels were found to develop larger, more non-polar molecules that failed in late stage ADME/Tox. Hits with adequate potency and low molecular weight (high ligand efficiency) and low clogP are now favored to progress.
Steven Frye, Director of the Center for Integrative Chemical Biology and Drug Discovery at UNC, Chapel Hill, rounded out the representation by discussing why academia should be involved in drug discovery. There are currently about 80 academic and not-for-profit centers for screening small molecules libraries. Some of these are fee-for-service, but it is likely that the long term sustainability of these centers will be reserved for those that function through collaborative efforts that produce chemical probes for further target validation, rather than those that generate leads for further progression in a drug discovery pipeline.
I believe academic and not-for-profit centers like NCGC provide hope for drug discovery going forward. Pharma is solving some of the problems of adverse pharmacokinetics/pharmacodynamics and toxicity by looking more at parameters like ligand efficiency, but efficacy remains a major source of drug attrition. This is inexorably linked to appropriate target validation. Generating tools like chemical probes for better target validation is just what the doctor ordered!
By, BioTek Instruments