Discovery of a Nanomolar Inhibitor of the Human Murine Double Minute 2 (MDM2)−p53 Interaction through an Integrated, Virtual Database Screening Strategy
Yipin Lu(University of Michigan–Ann Arbor), Zaneta Nikolovska‐Coleska(University of Michigan–Ann Arbor), Xueliang Fang(University of Michigan–Ann Arbor), Wei Gao(University of Michigan–Ann Arbor), Sanjeev Shangary(University of Michigan–Ann Arbor), Su Qiu(University of Michigan–Ann Arbor), Dongguang Qin(University of Michigan–Ann Arbor), Shaomeng Wang(University of Michigan–Ann Arbor)
Cited by 115Open Access
Abstract
An integrated, virtual database screening strategy has led to 7-[anilino(phenyl)methyl]-2-methyl-8-quinolinol (4, NSC 66811) as a novel inhibitor of the murine double minute 2 (MDM2)-p53 interaction. This quinolinol binds to MDM2 with a Ki of 120 nM and activates p53 in cancer cells with a mechanism of action consistent with targeting the MDM2-p53 interaction. It mimics three p53 residues critical in the binding to MDM2 and represents a promising new class of non-peptide inhibitors of the MDM2-p53 interaction.