BVD-523 (Ulixertinib) is a potent, selective, reversible, ATP-competitive ERK1/2 inhibitor with Ki of 0.3/0.04 nM, respectively.
BVD-523 demonstrated excellent ERK1/2 kinase selectivity based on biochemical counter-screens against 75 kinases.
BVD-523 inhibits cellular proliferation and enhances caspase-3/7 activity in vitro while demonstrating substrate inhibition despite increased ERK1/2 phorphorylation.
BVD-523 (25-100 mg/kg, PO, BID) demonstrates in vivo antitumor activity in BRAFV600E-mutant cancer cell line (A375 cell line) xenograft models, and dose-dependent antitumor activity in KRASG12C-mutant pancreatic cell line xenograft model, MIAPaCa2.
BVD-523 yielded synergistic antiproliferative effects in a BRAFV600E-mutant melanoma cell line xenograft model when used in combination with BRAF inhibition.
