SF-3-030

SF-3-030 is a potent and selective ERK1/2 inhibitor that does not compete with ATP. It selectively induces apoptosis in melanoma cells with mutant BRaf and continuously active ERK1/2 signaling. In mouse models of asthma, SF-3-030 alleviates various pathological features of the condition. This compound is useful for research on asthma and melanoma.

SF-3-030 selectively inhibits ERK2-mediated phosphorylation of the c-Fos F-site Thr325 residue in vitro at concentrations of 2.5-60 μM for 30 minutes, without affecting substrates with a D-domain (RSK1) or p38α-mediated ATF2 phosphorylation. At 1-100 μM for periods ranging from 20 minutes to 5 hours, it suppresses AP-1 and SRE promoter activities in EGF/PMA-stimulated HeLa/HEK293 cells and reduces basal AP-1 activity in A375 melanoma cells, showing greater potency against PMA-induced responses than EGF-induced responses. SF-3-030 at 5-100 μM for 30 minutes to 1 hour selectively inhibits expression of F-site containing immediate early genes (c-Fos, Fra1, FosB, FosB2, c-Myc) in EGF/PMA-stimulated HeLa and A375 cells, with minimal impact on non-F-site genes (c-Jun, Egr1). Furthermore, at 1-100 μM for 24 hours, the compound selectively inhibits proliferation and induces apoptosis in melanoma cells (A375, RPMI7951) with constitutive ERK1/2 activity, yielding GI50 values of 7.1 and 4.6 μM, while showing selectivity in Jurkat cells with GI50 > 50 μM.

Administering SF-3-030 (10 mg/kg; intranasally; 30 minutes prior to each HDM challenge; 5 days a week, for 3 weeks) alleviates several pathological features in a mouse model of asthma induced by house dust mite (HDM).