Packman Kathryn E

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: Overall, ATSP-7041 demonstrates in vitro and in vivo proof-of-concept that stapled peptides can be developed as therapeutically relevant inhibitors of protein–protein interaction and may offer a viable modality for cancer therapy.

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: In several tumor xenograft models of BRAF(V600E)-expressing melanoma, it was found that RG7204 treatment caused partial or complete tumor regressions and improved animal survival, in a dose-dependent manner, and no toxicity observed in any dose group in any of the in vivo models tested.

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.