In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor

Bioorganic & Medicinal Chemistry Letters
Andrea VaupelPascal Furet

Abstract

Small molecule inhibitors of the p53-MDM2 protein complex are under intense investigation in clinical trials as anti-cancer agents, including our first generation inhibitor NVP-CGM097. We recently described the rational design of a novel pyrazolopyrrolidinone core as a new lead structure and now we report on the synthesis and optimization of this to provide a highly potent lead compound. This new compound displayed excellent oral efficacy in our preclinical mechanistic in vivo model and marked a significant milestone towards the identification of our second generation clinical candidate NVP-HDM201.

Citations

Nov 5, 2019·Journal of Computer-aided Molecular Design·Zhonghua XiaIgor V Tetko
Jul 9, 2020·International Journal of Molecular Sciences·Nidhi Singh, Wenjin Li
Jan 12, 2021·European Journal of Medicinal Chemistry·Sergio AlgarRosario González-Muñiz

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