10.3389/fphar.2019.00818.s001 Kangni Wu Kangni Wu Yanghui Xiu Yanghui Xiu Pan Zhou Pan Zhou Yan Qiu Yan Qiu Yuhang Li Yuhang Li DataSheet_1_A New Use for an Old Drug: Carmofur Attenuates Lipopolysaccharide (LPS)-Induced Acute Lung Injury via Inhibition of FAAH and NAAA Activities.docx Frontiers 2019 fatty acid amide hydrolase (FAAH) N-acylethanolamine acid amidase (NAAA) carmofur acute lung injury drug repurposing 2019-07-19 12:27:21 Dataset https://frontiersin.figshare.com/articles/dataset/DataSheet_1_A_New_Use_for_an_Old_Drug_Carmofur_Attenuates_Lipopolysaccharide_LPS_-Induced_Acute_Lung_Injury_via_Inhibition_of_FAAH_and_NAAA_Activities_docx/8965775 <p>Acute lung injury (ALI), characterized by a severe inflammatory process, is a complex syndrome that can lead to multisystem organ failure. Fatty acid amide hydrolase (FAAH) and N-acylethanolamine acid amidase (NAAA) are two potential therapeutic targets for inflammation-related diseases. Herein, we identified carmofur, a 5-fluorouracil-releasing drug and clinically used as a chemotherapeutic agent, as a dual FAAH and NAAA inhibitor. In Raw264.7 macrophages, carmofur effectively reduced the mRNA expression of pro-inflammatory factors, including IL-1β, IL-6, iNOS, and TNF-α, and down-regulated signaling proteins of the nuclear transcription factor κB (NF-κB) pathway. Furthermore, carmofur significantly ameliorated the inflammatory responses and promoted resolution of pulmonary injury in lipopolysaccharide (LPS)-induced ALI mice. The pharmacological effects of carmofur were partially blocked by peroxisome proliferator-activated receptor-α (PPARα) antagonist MK886 and cannabinoid receptor 2 (CB2) antagonist SR144528, indicating that carmofur attenuated LPS-induced ALI in a PPARα- and CB2-dependent mechanism. Our study suggested that carmofur might be a novel therapeutic agent for ALI, and drug repurposing may provide us effective therapeutic strategies for ALI.</p>