Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10592597 | Bioorganic & Medicinal Chemistry Letters | 2014 | 5 Pages |
Abstract
Capitalizing on crystal structure information obtained from a previous effort in the search for non peptide inhibitors of the p53-MDM2 interaction, we have discovered another new class of compounds able to disrupt this protein-protein interaction, an important target in oncology drug research. The new inhibitors, based on a tetra-substituted imidazole scaffold, have been optimized to low nanomolar potency in a biochemical assay following a structure-guided approach. An appropriate strategy has allowed us to translate the high biochemical potency in significant anti-proliferative activity on a p53-dependent MDM2 amplified cell line.
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Andrea Vaupel, Guido Bold, Alain De Pover, Thérèse Stachyra-Valat, Joanna Hergovich Lisztwan, Joerg Kallen, Keiichi Masuya, Pascal Furet,