An inhibitor of p38 MAPK
Skepinone-L is a selective inhibitor of p38 mitogen-activated protein kinase (MAPK) with IC50 value of 5 nM[1].
P38 MAPKs are a class of MAPK which are responsive for stress stimuli, such as heat shock and osmotic shock. They are involved in cell differentiation and apoptosis [1].
Skepinone-L is a ATP-competitive inhibitor of p38 MAPK [1]. For in vitro test, the phosphory?lation of heat shock protein 27 (HSP27) of the p38 MAPK pathway can be used as a marker to assess the activity of p38 MAPK. When HeLa cells were treated with anisomycin, skepinone-L showed dose-dependent inhibition of HSP27 phosphorylation with a cellular IC50 ~25 nM, which confirmed the inhibition of p38 MAPK. Additionally, in peripheral blood mononuclear cells (hPBMCs), treatment of skepinone-L resulted in the reduction of p38 MAPK downstream effectors including TNF-α, IL-1β and IL-10 [1].
In mouse model, oral administration of skepinone-L resulted in very high level of skepinone-L which was 240 nM and higher than the human whole-blood IC50 value of skepinone. Therefore, it resulted in the inhibition of TNF-α by 77% via the inhibition of upstream p38 MAPK. Thus, it demonstrated the pre?eminent pharmacodynamic properties of skepinone-L [1].
Reference:
[1].? Koeberle, S C et al., Skepinone-L is a selective p38 mitogen-activated protein kinase inhibitor. Nature Chemical Biology, 2012, 8(2), 141-143.
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