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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Biochemical and biophysical research communications, 495(1), 1432-1439 (2017-11-22)
Functional abnormal airway epithelial cells, along with activated inflammatory cells, resulting in chronic airway inflammation, are considered as the characteristic of asthma. Fatty Acid Binding Protein 4 (FABP4) takes part in glucose and lipid homeostasis, and also have an important
Goblet cell metaplasia and excessive mucus secretion associated with asthma, cystic fibrosis, and chronic obstructive pulmonary disease contribute to morbidity and mortality worldwide. We performed a high-throughput screen to identify small molecules targeting a transcriptional network critical for the differentiation
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