MEDI 243 |
| Beta-secretase is a leading target for the development of therapies to treat Alzheimer's disease. Despite intense research over the past decade, only recently have high-affinity drug-like inhibitors of beta-secretase emerged. Fragment based approaches to lead generation rely on identifying drug fragments that contain minimal functionality for binding to the target of interest. Using NMR methods, we screened a library of low molecular weight compounds to identify hits that bound to the active site of beta-secretase with affinities (IC50) of 1-5 mM. X-ray crystallography facilitated the rapid evolution of these weak hits into high affinity (IC50 <100 nM) drug leads. |
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Abeta Production Inhibitors: Progress Toward a Clinical Test of the Amyloid Hypothesis
9:00 AM-12:00 PM, Wednesday, August 22, 2007 BCEC -- 210 B/C, Oral
Division of Medicinal Chemistry |