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HDAC6 inhibition by CKD-506

ECCO 2019

CKD-506 has been found to have therapeutic effects in various colitis animal models. Therefore, this oral selective histone deacetylase 6 (HDAC6) inhibitor may exert beneficial effect in patients with Crohn’s disease and ulcerative colitis. The effect of CKD-506 on rheumatoid arthritis is already being evaluated in a clinical phase 2 study.

In the preclinical study presented at ECCO 2019, HDAC6 was overexpressed in colon tissue of patients with Crohn’s disease and ulcerative colitis [1]. In vitro, HDAC6 overexpression by plasmid DNA strongly induced the production of various inflammatory mediators, especially TNFα, IL-6, IP-10, and ROS production from macrophages. However, CKD-506 inhibited HDAC6-mediated inflammatory responses in macrophages through NF-κB and AP-1. In vivo, CKD-506 strongly inhibited disease activity indexes in DSS-, TNBS-, piroxicam- (IL-10−/−)-, and adaptive T cell transfer-mediated colitis. In acute colitis models, CK...

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