Gary Fairley

TL;DR: It is demonstrated that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras.

TL;DR: Multiple series of highly selective covalent ERK1/2 inhibitors informed by structure-based drug design (SBDD) are identified for potential in vitro and in vivo studies to assess the risks and or benefits of targeting this pathway through such a mechanism of action.

TL;DR: In this article, the authors describe the use of pyrazine derivatives of Formula (I) for the treatment of cell proliferative disorders, and describe processes for their preparation, pharmaceutical compositions containing them, and their use in the manufacture of a medicament for use in a pharmaceutical composition.

TL;DR: Number of alternative, novel scaffolds with potentially improved potency and physicochemical properties were found, and one such compound demonstrated pharmacodynamic knockdown of phosphorylation of AKT and downstream biomarkers in vivo and inhibition of tumor growth in a breast cancer xenograft model.

TL;DR: This article reports on the recent work to identify novel, potent, and selective reversible ERK1/2 inhibitors from a low-molecular-weight, modestly active, and highly promiscuous chemical start point, compound 4.