A novel ERK inhibitor has potent activity in NRAS-mutant melanoma cancer models

Introduction

NRAS mutations occur in 15-20% of mutant melanoma cancer patients. Currently there is no approved therapy for NRAS-mutant melanoma, an indication which is associated with aggressive clinical outcome and a poor prognosis.
The NRAS mutation leads to constitutive activation of the MAPK pathway. ERK is the primary downstream effector of MAPK and its direct inhibition may provide an attractive therapeutic approach for the treatment of NRAS-mutant
melanoma.
As previously described, using fragment-based drug discovery we have identified a novel and selective inhibitor of ERK which inhibits in vitro ERK catalytic activity as well as ERK phosphorylation1.
Here, we demonstrate the in vitro and in vivo activity of a novel, highly potent, elective ERK inhibitor in models of NRAS-mutant melanoma.