Ahmed M I Elfiky, Mohammed Ghiboub, Andrew Y F Li Yim, Ishtu L Hageman, Jan Verhoeff, Manon de Krijger, Patricia H P van Hamersveld, Olaf Welting, Iris Admiraal, Shafaque Rahman, Juan J Garcia-Vallejo, Manon E Wildenberg, Laura Tomlinson, Richard Gregory, Inmaculada Rioja, Rab K Prinjha, Rebecca C Furze, Huw D Lewis, Palwinder K Mander, Sigrid E M Heinsbroek, Matthew J Bell, Wouter J de Jonge
BACKGROUND AND AIMS: Histone deacetylase inhibitors (HDACi) exert potent anti-inflammatory effects. Because of the ubiquitous expression of HDACs, clinical utility of HDACi is limited by off-target effects. Esterase-sensitive motif (ESM) technology aims to deliver ESM-conjugated compounds to human mononuclear myeloid cells, based on their expression of carboxylesterase 1 (CES1). This study aims to investigate utility of an ESM-tagged HDACi in inflammatory bowel disease (IBD). METHODS: CES1 expression was assessed in human blood, in vitro differentiated macrophage and dendritic cells and Crohn's disease (CD) colon mucosa by mass cytometry, quantitative PCR and immunofluorescence staining respectively...
October 11, 2021: Journal of Crohn's & Colitis