Portal de Periódicos da CAPES

Discovery of RG7388, a Potent and Selective p53–MDM2 Inhibitor in Clinical Development

2013; American Chemical Society; Volume: 56; Issue: 14 Linguagem: Inglês

10.1021/jm400487c

1520-4804

Qingjie Ding, Zhuming Zhang, Jinjun Liu, Nan Jiang, Jing Zhang, Tina Morgan Ross, Xin‐Jie Chu, David Bartkovitz, Frank Podlaski, Cheryl A. Janson, Christian Tovar, Zoran Filipovic, Brian Higgins, Kelli Glenn, Kathryn Packman, Lyubomir T. Vassilev, Bradford Graves,

Ubiquitin and proteasome pathways

Restoration of p53 activity by inhibition of the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity.