DS03090629 is a potent, selective, ATP-competitive and orally available MEK1/2 inhibitor, shows high affinity for the MEK protein regardless of its phosphorylation status (npMEK (inactive) Kd=0.11 nM, and pMEK (active) Kd=0.15 nM).
DS03090629 is effective for BRAF-overexpressing melanoma cell lines (A375_mock, IC50=37.1 nM; A375_BRAF, IC50=74.3 nM).
DS03090629 exhibits tendencies to retain inhibitory activities against both WT MEK1 and F53L mutant against wild-type pMEK1 and mutated pMEK1 in a cell-free enzymatic assays.
DS03090629 is effective against not only BRAF-overexpressing cancers, but also MEK1-mutated cancer cells.
DS03090629 also exhibits superior efficacy against a melanoma cell line expressing mutant MEK1 protein compared with dabrafenib and trametinib.
DS03090629 (75 mg/kg, mpk, QD) combined with dabrafenib significantly inhibited ERK phosphorylation, induced tumor regression in the A375_mock or A375_BRAF xenograft models.