Zunsemetinib (CDD-450) is an orally active and selective p38α mitogen-activated protein kinase-activated protein kinase 2 (MK2) pathway inhibitor. Zunsemetinib can be used for the research of immuno-inflammatory diseases[1].
Zunsemetinib (1 and 10 μM; 1 hour; WT and NOM ID BMMs) has no effect on NLRP3 expression, but decreases IL-1β expression by promoting IL-1β mRNA degradation[1].Zunsemetinib (0.4 nM~1 μM; 16 hours; PBMC) reduces IL-1β secretion and promotes IL-1β mRNA instability[1].Zunsemetinib selectively blocks p38α MAPK activation of the proinflammatory kinase MK2 while sparing p38α activation of other effectors such as PRAK and ATF2. Zunsemetinib inhibits in vitro osteoclast formation induced by RANKL[1].
Zunsemetinib (1,000 ppm; p.o.) blocks LPS-induced TNF-α expression persisted for up to 4 weeks after dosing[1].Zunsemetinib (10 and 20 mg/kg; p.o.) increases bone density[1].Zunsemetinib prevents osteopenia in NOM IDc mice through inhibition of osteoclastogenesis[1].
[1]. Zunsemetinib (ATI-450) - Investigational oral MK2 pathway inhibitor
[2]. Aclaris Therapeutics Announces ATI-450 (MK2 pathway Inhibitor) publication in Journal of Experimental Medicine
[3]. Wang C, et al. Selective inhibition of the p38α MAPK-MK2 axis inhibits inflammatory cues including inflammasome priming signals. J Exp Med. 2018;215(5):1315-1325.