Download MendeleyTetra-substituted imidazoles as a new class of inhibitors of the p53-MDM2 interaction.
Vaupel, A., Bold, G., De Pover, A., Stachyra-Valat, T., Hergovich-Lisztwan, J., Kallen, J., Masuya, K., Furet, P.(2014) Bioorg Med Chem Lett 24: 2110-2114
- PubMed: 24704029
- DOI: https://doi.org/10.1016/j.bmcl.2014.03.039
- Primary Citation of Related Structures:
4OQ3 - PubMed 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.
Organizational Affiliation:
Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. Electronic address: [email protected].
