Welcome to SBS 2011 - SLAS

Gaylord Palms Resort and Convention Center | March 27–31, 2011 | Orlando, Florida, USA
Drug Discovery Focused on Neglected Diseases Through Initiatives
Funded by Governments, Foundations and Private Donors
Ken Duncan, Bill & Melinda Gates Foundation
Drug discovery is no longer exclusively carried out in the laboratories of Pharma companies, or carried out with the express
purpose of generating profit. Many organizations now undertake sophisticated research programs, often using different
models with extensive collaborations to achieve the critical mass and breadth of skills required to be successful. This has
been particularly true in drug discovery programs aimed at finding new treatments for rare diseases and the neglected
diseases that disproportionately affect people in developing countries, where Pharma interest has been low because of the
lack of a viable market to recoup investment. Governments and private foundations have stepped in to provide funding, and
this brings with it an obligation to make products available to those most in need at the lowest possible cost. Partnership with
industry using shared resources and funding through in-kind contribution has often been critical to success. This session will
focus on drug discovery programs being conducted in non-traditional environments or being carried out in non-traditional
ways. Examples of programs that have succeeded in finding new leads and drug candidates for the rare and neglected
diseases will be highlighted.
The Importance of Metabolic Status to Tuberculosis Drug Discovery
Clifton Barry, NIAID, NIH
One of the major hurdles in the discovery of new agents active against Mtb is the lack of fully validated targets that can be
starting points for structure based design efforts. In vitro screening conditions often employ environmental variables fixed
at non-physiological conditions resulting ultimately in a disappointing correlation between in vitro and in vivo activities of
compounds directed against particular targets. qHTS is a powerful tool for identifying hits that provides quantitative data
from a primary screen. We have employed qHTS to a systematically altered set of environmental conditions against a set of
bioactive compounds containing drugs with known mechanism of action. By monitoring variation in sensitivity across sets
of related agents with known targets we hope to assess the vulnerability of these targets across the major environmental
conditions thought to be important in in vivo growth of the TB bacillus as well as identifying compounds and families that
have novel targets important only under selected conditions to systematically explore target space in this important human
pathogen. Employing microarrays, whole-genome resequencing of drug-resistant mutants, and novel sources of biologically
active material allows mechanistic information to be inferred that can suggest areas of unique vulnerability under in vivo
conditions.
Screening for Novel Antimalarials
R. Kip Guy, St. Jude Children’s Research Hospital
There has historically been a dearth of chemotypes that can be used to drive drug development campaigns for malaria.
We utilized a phenotypic whole cell screen of erythrocytic co-cultures of malaria to identify novel chemical compounds
that suppressed growth of or killed malaria. Representative members of the hit set were carefully profiled in a number of
assays to understand selectivity, mechanism of action, and potential for development.
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