Holzer, Philipp, Masuya, Keiichi, Furet, Pascal, Kallen, Joerg, Valat, Therese-Marie, Ferretti, Stephane Raymond, Berghausen, Joerg, Bouisset-Leonard, Michele, Buschmann, Nicole, Pissot Soldermann, Carole, Rynn, Caroline, Ruetz, Stephan, Stutz, Stefan, Chene, Patrick, Jeay, Sebastien and Gessier, Francois (2015) Discovery of NVP-CGM097 - a highly potent and selective MDM2 inhibitor undergoing phase 1 clinical trials in p53wt tumors. Journal of Medicinal Chemistry, 58 (16). pp. 6348-6358.

Abstract

As a result of our efforts to discover novel p53-MDM2 protein-protein interaction inhibitors useful for treating cancer, the potent and selective MDM2 inhibitor NVP-CGM097 (1) with an excellent in vivo profile was selected as a clinical candidate and is currently in phase 1 clinical development. This article provides an overview of the discovery of this new clinical p53-MDM2 inhibitor. The following aspects are addressed: mechanism of action, scientific rationale, binding mode, medicinal chemistry, pharmacokinetic and pharmacodynamic properties and in vivo pharmacology/toxicology in preclinical species.

Item Type:	Article
Date Deposited:	13 Oct 2015 13:11
Last Modified:	13 Oct 2015 13:11
URI:	https://oak.novartis.com/id/eprint/25927