A selective p38 MAPK inhibitor
SB239063 is a potent and selective p38 MAPK inhibitor with an IC50 of 44 nM against p38α MAPK while exihibited no activity against the γ- and δ-kinase isoforms [1].
In vitro: In oxygen-glucose-deprived hippocampal slice cultures, treatment with 20 μM and 100 μM SB239063 significantly reduced the levels of the pro-inflammatory cytokine IL-1β and reduced cell death after oxygen-glucose deprivation and strikingly diminished microglia activation[2].
In vivo: Oral administration of 3–30 mg/kg SB 239063 given twice a day dose-dependently inhibited airway neutrophil infiltration and interleukin (IL)-6 levels 48 h after lipopolysaccharide (LPS) inhalation [1]. In a bleomycin-induced pulmonary fibrosis model rats, SB 239063 treatment (2.4 or 4.8 mg/day via osmotic pump) significantly inhibited bleomycin-induced right ventricular hypertrophy (indicative of secondary pulmonary hypertension) and increased in lung hydroxyproline synthesis (indicative of collagen synthesis and fibrosis) (1). In conscious guinea pigs, administration of SB 239063 (10 or 30 mg/kg p.o.) showed approximately 50% inhibition of OA-induced pulmonary eosinophil influx, measured by BAL 24 h after antigen(1). Orally administration of SB 239063 (30 mg/kg) attenuated IL-6 bronchoalveolar lavage fluid concentrations (> 90% inhibition) and MMP-9 activity (64% inhibition) measured 6 h after LPS exposure. In guinea pig cultured alveolar macrophages, SB 239063 inhibited LPS-induced IL-6 production with IC50 of 362 nM. In lipopolysaccharide-stimulated human peripheral blood monocytes, SB 239063 inhibited IL-1 and TNF-α production with an IC50 of 0.12 and 0.35 μM, respectively(1).
参考文献:
[1] Underwood D C, Osborn R R, Bochnowicz S, et al.? SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung[J]. American Journal of Physiology-Lung Cellular and Molecular Physiology, 2000, 279(5): L895-L902.
[2] Strassburger M, Braun H, Reymann K G.? Anti-inflammatory treatment with the p38 mitogen-activated protein kinase inhibitor SB239063 is neuroprotective, decreases the number of activated microglia and facilitates neurogenesis in oxygen–glucose-deprived hippocampal slice cultures[J]. European journal of pharmacology, 2008, 592(1): 55-61.
| Cell experiment [1]: | |
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Cell lines |
Human isolated whole blood |
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Preparation method |
The solubility of this compound in DMSO is > 18.4 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0.01 ~ 10 μM; 4 hrs |
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Applications |
In lipopolysaccharide-stimulated human whole blood, SB 239063 concentration-dependently inhibited the production of a series of inflammatory cytokines including IL-1, TNF-α, IL-8 and IL-6, with the IC50 values ranging from 0.02 to 0.09 μM. In contrast, SB 239063 only showed weak inhibition of IL-1ra production, with the IC50 value of ~ 2 μM. |
| Animal experiment [1]: | |
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Animal models |
A Bleomycin-induced pulmonary fibrosis rat model |
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Dosage form |
2.4 or 4.8 mg/day via osmotic pump |
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Applications |
In a Bleomycin-induced pulmonary fibrosis rat model, SB 239063 significantly inhibited Bleomycin-induced right ventricular hypertrophy (indicative of secondary pulmonary hypertension), and substantially attenuated Bleomycin-induced lung hydroxyproline synthesis (indicative of collagen synthesis and fibrosis). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Underwood D C, Osborn R R, Bochnowicz S, et al. SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung[J]. American Journal of Physiology-Lung Cellular and Molecular Physiology, 2000, 279(5): L895-L902. | |
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