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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development
Qingjie Ding1, Zhuming Zhang, Jin-Jun Liu
1Discovery Chemistry, ‡Discovery Technologies, §Discovery Oncology, ∥Non-Clinical Development, Roche Research Center, Hoffmann-La Roche, Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
Abstract:
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.
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