Binh Thanh Vu

TL;DR: In this article, the authors identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts.

TL;DR: It is found that the cell-cycle arrest function of the p53 pathway is preserved in multiple tumor-derived cell lines expressing wild-type p53, but many have a reduced ability to undergo p53-dependent apoptosis.

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: These findings offer a preclinical proof-of-concept that RG7112 is effective in treatment of solid tumors expressing wild-type p53, and a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies.

TL;DR: Investigation of the role of p53 phosphorylation on six key serine residues for p53 activation using nutlin-3, a recently developed small molecule MDM2 antagonist shows that it is not required for activation of p 53 target genes or biological responses in vivo.