Skepinone-L is an ATP-competitive inhibitor of p38 MAPK isoform p38α (IC50s = 5 nM) and p38β (97% inhibition at 1 μM). It has little effect on a range of other kinases, including p38γ and p38δ. Skepinone-L dose-dependently blocks the phosphorylation of heat shock protein 27 (HSP27), a p38 MAPK substrate, in response to stimulation with anisomycin in HeLa cells (IC50 = 25 nM) or TNF-α in THP-1 cells. At 1 μM, it prevents phosphorylation of cytosolic phospholipase A2 in platelets in response to collagen-related peptide or thrombin , blunting platelet secretion and aggregation.
Skepinone-L is a potent and highly selective inhibitor of p38 MAP kinase which impairs platelet activation and thrombus formation.
[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.
