10.1021/cb400740c.s001 Shan-Yu Fung Shan-Yu Fung Vladimir Sofiyev Vladimir Sofiyev Julia Schneiderman Julia Schneiderman Aaron F. Hirschfeld Aaron F. Hirschfeld Rachel E. Victor Rachel E. Victor Kate Woods Kate Woods Jeff S. Piotrowski Jeff S. Piotrowski Raamesh Deshpande Raamesh Deshpande Sheena C. Li Sheena C. Li Nicole J. de Voogd Nicole J. de Voogd Chad L. Myers Chad L. Myers Charlie Boone Charlie Boone Raymond J. Andersen Raymond J. Andersen Stuart E. Turvey Stuart E. Turvey Unbiased Screening of Marine Sponge Extracts for Anti-inflammatory Agents Combined with Chemical Genomics Identifies Girolline as an Inhibitor of Protein Synthesis American Chemical Society 2014 crude marine sponge extracts girolline chemical genomics approach IL TLR Elongation Factor 2 protein synthesis Marine Sponge Extracts Chemical Genomics Identifies Girolline 2014-01-17 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Unbiased_Screening_of_Marine_Sponge_Extracts_for_Anti_inflammatory_Agents_Combined_with_Chemical_Genomics_Identifies_Girolline_as_an_Inhibitor_of_Protein_Synthesis/2331193 Toll-like receptors (TLRs) play a critical role in innate immunity, but activation of TLR signaling pathways is also associated with many harmful inflammatory diseases. Identification of novel anti-inflammatory molecules targeting TLR signaling pathways is central to the development of new treatment approaches for acute and chronic inflammation. We performed high-throughput screening from crude marine sponge extracts on TLR5 signaling and identified girolline. We demonstrated that girolline inhibits signaling through both MyD88-dependent and -independent TLRs (i.e., TLR2, 3, 4, 5, and 7) and reduces cytokine (IL-6 and IL-8) production in human peripheral blood mononuclear cells and macrophages. Using a chemical genomics approach, we identified Elongation Factor 2 as the molecular target of girolline, which inhibits protein synthesis at the elongation step. Together these data identify the sponge natural product girolline as a potential anti-inflammatory agent acting through inhibition of protein synthesis.