product name Skepinone-L
Description: Skepinone-L is a selective and ATP-competitive inhibitor p38α-MAPK with IC50 of 5 nM. 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.
References: Nat Chem Biol. 2011 Dec 25;8(2):141-3; Cell Physiol Biochem. 2013;31(6):914-24.
425.42
Formula
C24H21F2NO4
CAS No.
1221485-83-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 85 mg/mL (199.8 mM)
Water: <1 mg/mL
Ethanol: 85 mg/mL (199.8 mM)
Solubility (In vivo)
0.5% methylcellulose: 30 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: Skepinone-L shows concentration-dependent inhibition of HSP27 (Ser82) phosphorylation through the p38 MAPK pathway with a cellular IC50 of approximately 25 nM, and also reduces concentrations of TNF-α, IL-1β and IL-10, regulated by p38 MAPK, with IC50 ranging from 30 to 50 nM. Skepinone-L (1 μM) abrogates the phosphorylation of platelet p38 MAPK substrate Hsp27 activated by stimulation with CRP, thrombin or thromboxane A2 analogue U-46619, and impairs platelet secretion and aggregation. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | 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. |
| Animal model | Mouse |
| Formulation & Dosage | Dissolved in methyl cellulose; 3 mg/kg; p.o. |
| References | Nat Chem Biol. 2011 Dec 25;8(2):141-3; Cell Physiol Biochem. 2013;31(6):914-24. |
