Pharmacophore- and structure-based approaches to the development of small molecule inhibitors for Bcl-2 family proteins and MAP kinases

MEDI 96

Xiyun Zhang, xiyun@burnham.org1, Michele F. Rega1, Jui-Wen Huang1, John Stebbins1, Barbara Becattini1, and Maurizio Pellecchia2. (1) Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, Pellecchia Lab, Building 10, Room 2804, 10901 North Torrey Pines Road, La Jolla, CA 92037, (2) The Burnham Institute for Medical Research
We will discuss general virtual screening strategies based on the combination of pharmacophore-based drug design and structure-based drug design for addressing the challenges inherent in the discovery of small molecule inhibitors for Bcl-xL and JNK. Developing small molecules that inhibit these targets is widely considered to be difficult, owing to the challenges involved in modulating protein–protein interactions (Bcl-xL) and in obtaining selective ATP mimics (JNK). Prospective hits were identified by virtual screening large compound libraries and several were verified as potential drug leads in the following-up experimental tests. These results suggest that our simple approaches may be used to discover inhibitors of several therapeutically relevant protein targets.
 

General Poster Session
7:00 PM-9:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster

Division of Medicinal Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006