SB 203580
SB203580, also called 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl) 1Himidazole [6], is a specific pyridinyl imidazole inhibitor of p38-MAPK (Mitogen-activated Protein Kinase) signaling pathway [1] [3]. It was competitive with ATP with a selectivity probably determined by nonconserved regions within or near the ATP binding pocket and a Ki of 21 nM [3]. It inhibits c-Raf with an IC50 of 2 mM in vitro [4].
p38 MAPK signaling pathway enables cells to generate a plethora of different effects to interpret a wide range of external signals and respond appropriately. There is a core of three protein kinases acting sequentially in this pathway to ensure the diversity and specificity in cellular outcomes [5].
Exposure to 30 mM SB203580 significantly decreased the resistance of L1210/VCR cells to vincristine accompanied by the LC50 value of vincristine changed from 3.2036±0.521 to 0.5576±0.082 mM. Exposure to 10 mM SB203580 slightly changed the value of the resistance index, accompanied by the LC50 values of SB203580 to sensitive L1210 cells and to resistant cells were 39.26±2.2 mM and 52.06±7.6 mM, respectively [1].
In vivo, administration of SB203580 alone 24 h before the permanent middle cerebral arterial occlusion abolished the isoflurane preconditioning-induced neuroprotection. After isoflurane exposure, administration of SB203580 decreased phosphorylated p38 MAPK. SB203580 inhibited anisomycin pretreatment-induced neuroprotection [6].
References:
[1]. Miroslav Baranclk, Vierka Bohacova, Janka Kvackajova, et al. SB203580, a specific inhibitor of p38-MAPK pathway, is a new reversal agent of P-glycoprotein-mediated multidrug resistance. European Journal of Pharmaceutical Sciences, 2001, 14: 29-36.
[2]. Shuqiu Zheng and Zhiyi Zuo. Isoflurane Preconditioning Induces Neuroprotection against Ischemia via Activation of P38 Mitogen-Activated Protein Kinases. Molecular Pharmacology, 2004, 65:1172-1180.
[3]. Peter R. Young, Megan M. McLaughlin, Sanjay Kumar, et al. Pyridinyl Imidazole Inhibitors of p38 Mitogen-activated Protein Kinase Bind in the ATP Site. The Journal of Biological Chemistry, 1997, 272(18): 12116-12121.
[4]. Clare A Hall-Jackson, Michel Goedert, Philip Hedge, et al. E?ect of SB 203580 on the activity of c-Raf in vitro and in vivo. Oncogene, 1999, 18: 2047-2054.
[5]. Ana Cuadrado and Angel R. Nebreda. Mechanisms and functions of p38 MAPK signalling. Biochem. J., 2010, 429: 403-417.
[6]. Shuqiu Zheng and Zhiyi Zuo. Isoflurane Preconditioning Induces Neuroprotection against Ischemia via Activation of P38 Mitogen-Activated Protein Kinases. Mol Pharmacol, 2004, 65: 1172-1180.
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| Storage | Desiccate at 4°C |
| M.Wt | 377.44 |
| Cas No. | 152121-47-6 |
| Formula | C21H16FN3OS |
| Solubility | insoluble in H2O; ≥18.872 mg/mL in DMSO; ≥3.28 mg/mL in EtOH with ultrasonic |
| Chemical Name | 4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine |
| SDF | Download SDF |
| Canonical SMILES | CS(=O)C1=CC=C(C=C1)C2=NC(=C(N2)C3=CC=NC=C3)C4=CC=C(C=C4)F |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
Sf9 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. 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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Reaction Conditions |
IC50: 2 μM, |
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Applications |
Human c-Raf was activated in Sf9 cells by cotransfection with DNA encoding v-Ras and Lck, and activity was either measured directly in the cell lysates or after immunoprecipitation. The c-Raf in Sf9 cell extracts is inhibited by SB 203580 with an IC50 value of 2 μM. This is 40-fold higher than the IC50 for SAPK2a/p38α, but only four-fold higher than the IC50 for SAPK2b/p38β2. However, the IC50 values became 10-fold higher if the assays were carried out using c-Raf immunoprecipitated from Sf9 cells, EGF-stimulated mouse Swiss 3T3 cells or EGF-stimulated 293 cells. |
| Animal experiment: [2] | |
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Animal models |
Female Brown Norway rats |
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Dosage form |
Oral administration, 10-100 mg/kg |
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Applications |
Oral administration of SB 203580 (10-100 mg/kg) had no significant effect on airway eosinophilia in comparison to the vehicle treated, challenged group. No reduction in BAL neutrophilia was observed after administration of SB 203580. In the lung tissue the basal numbers of neutrophils were not altered by pretreatment with SB 203580. The basal number of BAL monocytes/macrophages were unaffected by SB 203580 (unchallenged, vehicle 443.8±36.2: challenged, vehicle 414.1±29.7: challenged, SB 203580 100 mg/kg 381.5±41.86103 cells ml-1). However, SB 203580 produced a dose-related increase in lung tissue monocyte/macrophage cell numbers. |
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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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References: [1] Hall-Jackson C A, Goedert M, Hedge P, et al. Effect of SB 203580 on the activity of c-Raf in vitro and in vivo. Oncogene, 1999, 18(12): 2047-2054. [2] Escott K J, Belvisi M G, Birrell M A, et al. Effect of the p38 kinase inhibitor, SB 203580, on allergic airway inflammation in the rat. British journal of pharmacology, 2000, 131(2): 173-176. |
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| Description | SB203580 is a p38 inhibitor of MAPK with IC50 of 0.3-0.5 μM, 10-fold less sensitive to SAPK3(106T) and SAPK4(106T) and blocks PKB phosphorylation with IC50 of 3-5 μM. | |||||
| Targets | p38 MAPK | PKB | ||||
| IC50 | 0.3–0.5 μM | 3–5 μM | ||||
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