Discovery of RG7388, a Potent and Selective p53鈥揗DM2 Inhibitor in Clinical Development
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- 作者：Qingjie Ding ; Zhuming Zhang ; Jin-Jun Liu ; Nan Jiang ; Jing Zhang ; Tina M. Ross ; Xin-Jie Chu ; David Bartkovitz ; Frank Podlaski ; Cheryl Janson ; Christian Tovar ; Zoran M. Filipovic ; Brian Higgins ; Kelli Glenn ; Kathryn Packman ; Lyubomir T. Vassilev ; Bradford Graves
- 刊名：Journal of Medicinal Chemistry
- 出版年：2013
- 出版时间：July 25, 2013
- 年：2013
- 卷：56
- 期：14
- 页码：5979-5983
- 全文大小：324K
- 年卷期：v.56,no.14(July 25, 2013)
- ISSN：1520-4804
文摘
Restoration of p53 activity by inhibition of the p53鈥揗DM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein鈥損rotein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53鈥揗DM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity.