In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor.
Basic Information
ID: ALA4265923
Journal: Bioorg Med Chem Lett
Title: In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor.
Authors: Vaupel A, Holzer P, Ferretti S, Guagnano V, Kallen J, Mah R, Masuya K, Ruetz S, Rynn C, Schlapbach A, Stachyra T, Stutz S, Todorov M, Jeay S, Furet P.
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.
CiteXplore: 30217415
DOI: 10.1016/j.bmcl.2018.08.027
Patent ID: ┄