NFX-179 (Nedometinib, NFX179) is a potent, specific, topical, metabolically labile MEK1/2 inhibitor with biochemical IC50 of 135 nM (MEK1).
NFX-179 is specific for MEK1 inhibition and does not have substantial interactions across a panel of more than 150 kinases or a separate panel of 44 targets of particular relevance for neurological or cardiac toxicity.
NFX-179 potently inhibits phosphorylated-ERK (p-ERK) expression in a malignant peripheral nerve sheath tumor cell line HCT116 (KRAS-mutant G13D) and A375 (BRAF-mutant V600E) with IC50 of 164 nM and 12 nM, respectively.
NFX-179 gel (topical application) significantly reduced the formation of new cSCCs in ultraviolet-induced cSCC mouse models.
NFX-179 inhibits the growth of human SCC cell lines in a dose-dependent manner, and topical NFX-179 application penetrates human skin and inhibits MAPK signaling in human cutaneous squamous cell carcinoma (cSCC) explants.