Novel small molecules were designed to specifically target the ligand-binding pocket of a PDZ domain. Iterative molecular docking and modeling allowed the design of an indole scaffold 10a as a reversible inhibitor of ligand binding. The 10a scaffold inhibited the interaction between MAGI-3 and PTEN and showed cellular activities that are consistent with the inhibition of NHERF-1 function.
|Number of pages||4|
|Journal||Bioorganic and Medicinal Chemistry Letters|
|State||Published - Jan 15 2007|
Bibliographical noteFunding Information:
We thank Angela McArthur for scientific editing of the manuscript. Financial support was provided in part by the Fujisawa Pharmaceutical Co., Ltd. (NF), the UCSF Stuart Trust Fund (NF, KAN, RKG), the Sandler Research Foundation, and the Sidney Kimmel Research Foundation (NF, RKG).
- Drug design
- PDZ domain
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry