An inhibitor of RIPK2
WEHI-345 is a potent and selective RIPK2 kinase inhibitor with an IC50 of 0.13 μM, which delays RIPK2 ubiquitylation and NF-κB activation on oligomerization domain (NOD) stimulation[1].
WEHI-345 (500 nM; Raw 267.4 cells) is able to inhibit MDP-induced autophosphorylation activity of RIPK2 in cells[1].WEHI-345 (500 nM; 0 hour, 2 hours, 4 hours, 8 hours; BMDMs or THP-1 cells) potently blocks MDP-induced transcription of the inflammatory mediators TNF and interleukin-6 (IL-6) in bone marrow-derived macrophages (BMDMs). In THP-1 cells, WEHI-345 reduces mRNA levels of NF-kB targets such as TNF, IL-8, IL-1b and A20[1].
WEHI-345 (20 mg/kg; intraperitoneal injection; twice daily; for 6 days; C57BL/6 male mice) treatment reduces disease score, inflammatory infiltrate, histological score and recruitment of dendritic cells to the site of inflammation. And improves body weight and reduces cytokine and chemokine levels, indicating an overall improvement of the condition in experimental autoimmune encephalomyelitis (EAE)-induced wild-type C57Bl/6 mice[1].
参考文献:
[1]. Nachbur U, et al. A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production. Nat Commun. 2015 Mar 17;6:6442.
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