Induces FOXM1 degradation and blocks its nuclear localization, suppresses FOXM1-mediated goblet cell metaplasia and airway hyperresponsiveness in vivo.
RCM-1 is a forkhead box M1 (FOXM1) inhibitor that blocks FOXM1 nuclear localization (IC50 = 720 nM using GFP-FOXM1-expressing U2OS cells) and causes FOXM1 degradation via ubiquitination induction (2.9- and 4.8-fold of basal level in A549 cells with 10 μM or 20 μM RCM-1, respectively) without affecting cellular YAP, FACT140, NF-κB, FOXA2, and FOXJ1 levels. RCM-1 intraperitoneal injection (1.7 mg/kg) in mice downregulates endogenous murine FOXM1 level as well as transgenic human FOXM1 GFP fusion level in vivo, effectively suppressing house dust mite-induced lung inflammation as well as goblet cell metaplasia and airway hyperresponsiveness in response to IL-13.
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