Kelli Glenn

TL;DR: The discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity is reported, with a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles.

TL;DR: RG7112 is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket ofMDM2, which stabilizes p53 and activates the p 53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts.

TL;DR: Preclinical results support evaluation of RO4929097 in clinical studies using an intermittent dosing schedule, and comparative microarray analysis suggests tumor cell differentiation as an additional mode of action.

TL;DR: Two new potent, selective, and orally active p53-MDM2 antagonists are reported, RO5353 and RO2468, as follow-ups with promising potential for clinical development.

TL;DR: It is demonstrated that administration of RG7112 in vivo in rats and monkeys results in thrombocytopenia and insight is provided into the role of the p53-MDM2 auto-regulatory loop in normal megakaryocytopoiesis.