4-[4-(4-fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-yl]phenol

• ChemBase ID: 72494
• Molecular Formular: C20H14FN3O
• Molecular Mass: 331.3430632
• Monoisotopic Mass: 331.1120903
• SMILES: c1c(ccc(c1)c1nc([nH]c1c1ccncc1)c1ccc(cc1)O)F
• Canonical SMILES: Oc1ccc(cc1)c1nc(c([nH]1)c1ccncc1)c1ccc(cc1)F
• InChI: InChI=1S/C20H14FN3O/c21-16-5-1-13(2-6-16)18-19(14-9-11-22-12-10-14)24-20(23-18)15-3-7-17(25)8-4-15/h1-12,25H,(H,23,24)
• InChIKey: QHKYPYXTTXKZST-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-[4-(4-fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-yl]phenol
• IUPAC Traditional name: 4-[4-(4-fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-yl]phenol
• Synonyms: 4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole; SB 202190; SB 202190; 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1h-imidazole

Database IDs

• CAS Number: 152121-30-7
• MDL Number: MFCD00941964
• PubChem SID: 24278272; 162037419
• PubChem CID: 5353940

CALCULATED PROPERTIES

• Acid pKa: 9.645799
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): 3.9184663
• LogD (pH = 7.4): 4.096198
• Log P: 4.1013126
• Molar Refractivity: 103.9327 cm^3
• Polarizability: 38.711132 Å^3
• Polar Surface Area: 61.8 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: DMSO; DMSO: soluble30 mg/mL
• Apperance: pale yellow

Safety Information

• Storage Condition: -20°C
• European Hazard Symbols: Irritant (Xi)
• German water hazard class: 3
• Risk Statements: 36/37/38
• Safety Statements: 26-36/37
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H315-H319-H335
• GHS Precautionary statements: P261-P305 + P351 + P338
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: p38 MAPK
• Gene Information: human ... MAPK14(1432)

Product Information

• Purity: ≥98% (HPLC); 97%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C20H14FN3O

DETAILS

Selleck Chemicals - S1077

Research Area

• Description: Inflammation

Biological Activity

• Description: SB 202190 (FHPI) is a potent p38 MAPK inhibitor targeting p38α and p38β with IC50 of 50 nM and 100 nM, respectively.
• Targets: p38α; p38β
• IC50: 50 nM; 100 nM ^[1]
• In Vitro: SB 202190 significantly inhibits both basal and anti-Fas antibody-induced MAPKAPK 2 activity in a dose-dependent manner. SB202190 by itself is sufficient to induce cell death in Jurkat and HeLa cells through activation of CPP32-like caspases, which can be blocked by expression of bcl-2. SB202190-induced apoptosis is attenuated by p38β but augmented by p38α. ^[2] SB 202190 strongly inhibits UVB induced COX-2 protein expression in HaCaT cells, and markedly inhibits UVB induced cox-2 mRNA. ^[3] SB 202190 treatment inhibits the expression of albumin-induced proinflammatory (monocyte chemoattractant protein-1) and transforming growth factor (TGF)-beta1-induced profibrotic (procollagen-Ialpha1) genes over 50% in renal tubular cells (normal rat kidney-52E). ^[4] SB 202190 treatment induces phosphorylation of JNK in a dose- and time- dependent manner in A549 cells, induces phosphorylation of ATF-2 transcription factor, and increases AP-1 DNA binding. ^[6] SB 202190 treatment enhances the growth of THP-1 and MV4-11 cells. SB 202190 increases the phosphorylation of c-Raf and ERK, suggesting that Ras-Raf-MEK-mitogen-activated protein kinase (MAPK) pathway activation is involved in the leukemia cell growth induced by SB 202190. ^[7]
• In Vivo: Inhibiting p38 by administration of SB 202190 inhibits PV IgG-induced blister formation in the passive transfer mouse model. ^[5] In the endotoxin model of sepsis, SB 202190 treatment produces a statistically significant survival benefit compared with control. ^[8]

Combination Therapy

• Description: The p38 inhibition by SB 202190 sensitizes tumor cells derived from both SN38-sensitive and -resistant HCT116 cells to Irinotecan treatment in xenograft models. ^[9] SB 202190 significantly decreases the Etoposide-induced ERCC1 protein levels and DNA repair capacity in etoposide-exposed NSCLC cells to sensitize lung cancer cells to Etoposide. ^[10]

Protocol

• Protocol: Kinase Assay ^[1]
• In vitro kinase assays: The p38α and p38β are assayed in 25 mM Tris-HCl, pH 7.5, containing 0.1 mM EGTA, with myelin basic protein (0.33 mg/mL) as substrate. Assays are performed either manually for 10 minutes at 30 °C in 50 μL incubations using [γ-^33P]ATP, or with a Biomek 2000 Laboratory Automation Workstation in a 96-well format for 40 minutes at ambient temperature in 25 μL incubations using [γ-^33P]ATP. The concentrations of ATP and magnesium acetate are 0.1 mM and 10 mM respectively. All assays are initiated with MgATP. Manual assays are terminated by spotting aliquots of incubation on to phosphocellulose paper, followed by immersion in 50 mM phosphoric acid. Robotic assays are terminated by the addition of 5 μL of 0.5 M phosphoric acid before spotting aliquots on to P30 filter mats. All papers are then washed four times in 50 mM phosphoric acid to remove ATP, once in acetone (manual incubations) or methanol (robotic incubations), and then dried and counted for radioactivity.
• Protocol: Cell Assay ^[2]
• Cell Lines: Jurkat, and HeLa
• Concentrations: Dissolved in DMSO, final concentrations ~50 μM
• Incubation Time: 24 hours
• Methods: Cells are serum-starved and then treated with different concentration of SB 202190 for 24 hours. Cell viability is assayed by either trypan blue exclusion or propidium iodide exclusion followed by flow cytometry analysis. The apoptotic nuclei are visualized by H33258 staining.
• Protocol: Animal Study ^[5]
• Animal Models: C57BL/6J mice injected i.d. with a sterile solution of either control IgG or PV IgG
• Formulation: Dissolved in DMSO, and diluted in saline
• Doses: 12.5 μg
• Administration: Administered via i.d.

References

• References: [1] Davies SP, et al. Biochem J, 2000, 351(Pt 1), 95-105.
• References: [2] Nemoto S, et al. J Biol Chem, 1998, 273(26), 16415-16420.
• References: [3] Chen W, et al. Oncogene, 2001, 20(29), 3921-3926.
• References: [4] Prakash J, et al. J Pharmacol Exp Ther, 2006, 319(1), 8-19.
• References: [5] Berkowitz P, et al. Proc Natl Acad Sci U S A, 2006, 103(34), 12855-12860.
• References: [6] Muniyappa H, et al. Cell Signal, 2008, 20(4), 675-683.
• References: [7] Hirosawa M, et al. Leuk Res, 2009, 33(5), 693-699.
• References: [8] O'Sullivan AW, et al. J Surg Res, 2009, 152(1), 46-53.
• References: [9] Paillas S, et al. Cancer Res, 2011, 71(3), 1041-1049.
• References: [10] Tsai MS, et al. Mol Cancer Ther, 2012, 11(3), 561-571.

Sigma Aldrich - S7067

Biochem/physiol Actions
SB 202190 is a highly selective, potent and cell permeable inhibitor of p38 MAP kinase. SB 202190 binds within the ATP pocket of the active kinase (Kd = 38 nM, as measured in recombinant human p38), and selectively inhibits the p38α and β isoforms.
Legal Information
Sold for research purposes under agreement from Glaxo-Smith-Kline

REFERENCES

• Prakash J, et al. J Pharmacol Exp Ther, 2006, 319(1), 8-19.
• Paillas S, et al. Cancer Res, 2011, 71(3), 1041-1049.
• Berkowitz P, et al. Proc Natl Acad Sci U S A, 2006, 103(34), 12855-12860.
• Muniyappa H, et al. Cell Signal, 2008, 20(4), 675-683.
• Hirosawa M, et al. Leuk Res, 2009, 33(5), 693-699.
• O'Sullivan AW, et al. J Surg Res, 2009, 152(1), 46-53.
• Tsai MS, et al. Mol Cancer Ther, 2012, 11(3), 561-571.
• Davies SP, et al. Biochem J, 2000, 351(Pt 1), 95-105.
• Nemoto S, et al. J Biol Chem, 1998, 273(26), 16415-16420.
• Chen W, et al. Oncogene, 2001, 20(29), 3921-3926.