1448866-66-7Relevant articles and documents
In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor
Vaupel, Andrea,Holzer, Philipp,Ferretti, Stephane,Guagnano, Vito,Kallen, Joerg,Mah, Robert,Masuya, Keiichi,Ruetz, Stephan,Rynn, Caroline,Schlapbach, Achim,Stachyra, Thérèse,Stutz, Stefan,Todorov, Milen,Jeay, Sébastien,Furet, Pascal
, p. 3404 - 3408 (2018/09/17)
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.