SB 203580 Chemical Properties

Melting point:

144-146

Boiling point:

615.6±55.0 °C(Predicted)

Density 

1.4

storage temp. 

-20°C

solubility 

DMSO: 50 mg/mL

pka

9.60±0.10(Predicted)

form 

solid

color 

white to off-white

Stability:

-200C

InChI

InChI=1S/C21H16FN3OS/c1-27(26)18-8-4-16(5-9-18)21-24-19(14-2-6-17(22)7-3-14)20(25-21)15-10-12-23-13-11-15/h2-13H,1H3,(H,24,25)

InChIKey

CDMGBJANTYXAIV-UHFFFAOYSA-N

SMILES

C1=NC=CC(C2NC(C3=CC=C(S(C)=O)C=C3)=NC=2C2=CC=C(F)C=C2)=C1

CAS DataBase Reference

152121-47-6(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xn

Risk Statements 

22-41

Safety Statements 

26-39

WGK Germany 

3

HS Code 

29333990

MSDS

• Language:English Provider:SigmaAldrich

SB 203580 Usage And Synthesis

Description

SB 203580 (152121-47-6) is a potent and selective inhibitor of p38 MAP kinase, IC50=50 and 500 nM for p38 and p38β2 respectively.1 No other kinases (in a panel of 30) were significantly inhibited including p38γ and δ at 10 μM.2?A potent inhibitor of inflammatory cytokine production (IC50=15-25 mg/kg in mice and rats) in animal models of arthritis, bone resorption, endotoxin shock and immune function.3

Chemical Properties

White to Off-White Solid

Uses

A pyridinyl imidazole which acts as a specific inhibitor of p38 MAP kinase. Does not inhibit the MAP kinase homologs JNK and p42 MAP kinase

Uses

A p38 MAPK inhibitor with an IC50 range of 0.3-0.5 μM and blocks PKB phosphorylation with an IC50 range of 3-5 μM.

Uses

MDCK cells were treated with SB 203580 to study the role of MAPK signaling in inducing hypertonicity of cell membrane and potassium depletion.¹⁶ It was used to inhibit MAPK signaling in mouse cortical neurons¹⁷ and human hepatocellular carcinoma cell lines.¹⁸

Definition

ChEBI: A member of the class of imidazoles carrying 4-methylsulfinylphenyl, 4-pyridyl and 4-fluorophenyl substituents at positions 2, 4 and 5 respectively. An inhibitor of mitogen-activated protein kinase.

General Description

Reduces epirubicin-induced cell injury and caspase-3/7 activity. A highly specific, potent, cell-permeable, selective, reversible, and ATP-competitive inhibitor of p38 kinase (IC₅₀ = 34 nM in vitro, 600 nM in cells). Also known as reactivating kinase (RK) and CSBP (cytokine synthesis anti-inflammatory drug binding protein). Does not significantly inhibit JNK or p42 MAP kinase even at 100 μM. Inhibits IL-1 and TNF-α production from LPS-stimulated human monocytes and the human monocyte cell line THP-1 (IC₅₀ = 50-100 nM). SB 203580 has also been shown to be an effective inhibitor of inflammatory cytokine production in vivo in both mice and rats.

Biological Activity

Water-soluble salt of SB 203580 (4-[5-(4-Fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazol-4-yl]pyridine ). Selective inhibitor of p38 mitogen-activated protein kinase (IC 50 values are 50 and 500 nM for SAPK2a/p38 and SAPK2b/p38 β 2 respectively). Displays 100-500-fold selectivity over LCK, GSK3 β and PKB α . Shown to inhibit interleukin-2-induced T-cell proliferation, cyclooxygenase-1 and -2, and thromboxane synthase.

Biochem/physiol Actions

SB 203580 is a pyridinyl imidazole that suppresses the activation of MAPKAP kinase-2 and inhibits the phosphorylation of heat shock protein (HSP) 27 in response to IL-1, cellular stresses and bacterial endotoxin in vivo. It does not inhibit JNK or p42 MAP kinase and therefore, is useful for studying the physiological roles and targets of p38 MAPK and MAPKAP kinase-2. It has been shown to induce the activation of the serine/threonine kinase Raf-1 and has been reported to inhibit cytokine production.

storage

+4°C (desiccate)

Background

p38 MAP kinase, also called RK or CSBP, is the mammalian orthologue of the yeast HOG kinase that participates in a signaling cascade controlling cellular responses to cytokines and stress. Four isoforms of p38 MAPK, p38α, β, γ, and δ have been identified. Similar to the SAPK/JNK pathway, p38 MAPK is activated by a variety of cellular stresses, including osmotic shock, inflammatory cytokines, lipopolysaccharide, UV light, and growth factors. MKK3, MKK6, and SEK activate p38 MAPK by phosphorylation at Thr180 and Tyr182. Activated p38 MAPK has been shown to phosphorylate and activate MAPKAP kinase 2 and to phosphorylate the transcription factors ATF-2, Max, and MEF2. SB203580-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-imidazole) is a selective inhibitor of p38 MAPK. This compound inhibits the activation of MAPKAPK-2 by p38 MAPK and subsequent phosphorylation of HSP27. SB203580 inhibits p38 MAPK catalytic activity by binding to the ATP-binding pocket, but does not inhibit phosphorylation of p38 MAPK by upstream kinases.

References

[1] ANA CUENDA . SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1[J]. FEBS Letters, 1995, 364 2: Pages 229-233. DOI:10.1016/0014-5793(95)00357-f
[2] S. DAVIES. Specificity and mechanism of action of some commonly used protein kinase inhibitors.[J]. The Ukrainian Biochemical Journal, 2000, 24 1: 95-105. DOI:10.1042/bj3510095
[3] A M BADGER. Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function.[J]. Journal of Pharmacology and Experimental Therapeutics, 1996, 279 3: 1453-1461.

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