SKLB-D18 is a first-in-class potent dual ERK1/2 and ERK 5 inhibitor (IC50s: ERK1 = 39 nM, ERK2 = 40 NM, ERK5 = 60 nM) and is highly selective against a panel of 380 kinases. It exhibited good activity against MDA-MB-231 (IC50 = 0.93 µM) and MDA-MB-468 (IC50 = 1.05 µM) cells. SKLB-D18 inhibited activation of ERK1/2/5 downstream components p-ERK5, p-RSK90, p-c-Myc, and c-MYC. It was also able to induce autophagy-dependent cell death and ferroptosis in triple negative breast cancer cells. Active in mouse triple negative breast cancer xenografts.
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