SB239063 (SB-239063) is a novel, highly potent, orally bioactive and selective p38 MAPKα/β inhibitor with potential anti-inflammatory activity. With an IC50 of 44 nM, it inhibits p38 MAPKα/β but exhibits little or no activity against the p38 MAPK γ- and δ-isoforms. SB 239063 is approximately three times more selective than SB 203580 and exhibits > 220 fold selectivity for p38 MAPK over ERK, JNK1, and other kinases. Interleukin-1 and tumor necrosis factor-alpha production in human peripheral blood monocytes stimulated with LPS was inhibited by SB 239063 (IC(50) values: 0.12 and 0.35 microM, respectively). SB 239063 might be helpful in the management of inflammatory conditions such as asthma.

Physicochemical Properties

Molecular Formula	C20H21FN4O2
Molecular Weight	368.4
Exact Mass	368.165
Elemental Analysis	C, 65.20; H, 5.75; F, 5.16; N, 15.21; O, 8.69
CAS #	193551-21-2
Related CAS #	193551-21-2
PubChem CID	5166
Appearance	White to yellow solid powder
Density	1.35g/cm3
Boiling Point	594.8ºC at 760 mmHg
Flash Point	313.5ºC
Vapour Pressure	5.42E-15mmHg at 25°C
Index of Refraction	1.655
LogP	3.63
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	27
Complexity	469
Defined Atom Stereocenter Count	0
SMILES	FC1C([H])=C([H])C(=C([H])C=1[H])C1=C(C2C([H])=C([H])N=C(N=2)OC([H])([H])[H])N(C([H])=N1)C1([H])C([H])([H])C([H])([H])C([H])(C([H])([H])C1([H])[H])O[H]
InChi Key	ZQUSFAUAYSEREK-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H21FN4O2/c1-27-20-22-11-10-17(24-20)19-18(13-2-4-14(21)5-3-13)23-12-25(19)15-6-8-16(26)9-7-15/h2-5,10-12,15-16,26H,6-9H2,1H3
Chemical Name	4-[4-(4-fluorophenyl)-5-(2-methoxypyrimidin-4-yl)imidazol-1-yl]cyclohexan-1-ol
Synonyms	SB 239063; SB-239063; SB239063
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	p38α (IC50 = 44 nM); p38β (IC50 = 44 nM)
ln Vitro	SB 239063 potently inhibits IL-1 and TNF-α production in LPS-stimulated human peripheral blood monocytes with IC50 of 120 and 350 nM, respectively. [1] In oxygen-glucose deprived hippocampal slice cultures, SB239063 causes cell death after oxygen-glucose deprivation and significantly lowers microglia activation. It also dramatically lowers the levels of the pro-inflammatory cytokine IL-1beta. [2] SB 239063 prevents TGF-β(2) and FGF-2-induced cell migration in human corneal endothelial cells. [4]
ln Vivo	SB 239063 (10 mg/kg, p.o.) lessens antigen-induced eosinophilia in the airways of mice and guinea pigs. [1] SB239063 prevents bronchial contraction in C57/BL6 and MKP-1(-/-) mice that have been exposed to air and ozone. [3]
Enzyme Assay	SB 239063 is a potent and selective p38 MAPK inhibitor (IC50 = 44 nM for p38α). It displays > 220-fold selectivity over ERK, JNK1 and other kinases; and is ~ 3-fold more selective than SB 203580.
Cell Assay	Apoptosis assay[1] Cell Types: Eosinophils (guinea pig BALs) Tested Concentrations: 0.1, 1, 10 μM Incubation Duration: 29, 47 hrs (hours) Experimental Results: Increased apoptosis of eosinophils in a dose-dependent manner in the presence of 10 pM IL-5 at every time point from 21 hours onwards. Treatment with 20 μM and 100 μM SB239063 significantly decreased the levels of the pro-inflammatory cytokine IL-1β, decreased cell death following oxygen-glucose deprivation, and dramatically decreased microglia activation in hippocampal slice cultures.
Animal Protocol	Animal/Disease Models: Male BALB/c mice (18–20 g) [1] Doses: 12 mg/kg Route of Administration: Oral gavage; 1 h before and 4 h after OA challenge; bis in die for 3 days Experimental Results: dramatically inhibited the resultant antigen-induced airway eosinophilia. Guinea pigs [5] ~30 mg/kg p.o. In guinea pig cultured alveolar macrophages, SB 239063 inhibited LPS-induced IL-6 production (IC(50) of 362 nM). In a bleomycin-induced pulmonary fibrosis model in rats, treatment with SB 239063 (2.4 or 4.8 mg/day via osmotic pump) significantly inhibited bleomycin-induced right ventricular hypertrophy (indicative of secondary pulmonary hypertension) and increases in lung hydroxyproline synthesis (indicative of collagen synthesis and fibrosis). Therefore, SB 239063 demonstrates activity against a range of sequelae commonly associated with COPD and fibrosis, supporting the therapeutic potential of p38 MAPK inhibitors such as SB 239063 in chronic airway disease [5].
References	[1]. J Pharmacol Exp Ther. 2000 Apr;293(1):281-8. [2]. Eur J Pharmacol. 2008 Sep 11;592(1-3):55-61. [3]. Eur Respir J. 2011 Apr;37(4):933-42. [4]. Exp Eye Res. 2013 Mar:108:23-32. [5]. Am J Physiol Lung Cell Mol Physiol. 2000 Nov;279(5):L895-902.
Additional Infomation	SB-239063 is a member of the class of imidazoles carrying 4-hydroxycyclohexyl, 4-fluorophenyl and 2-methoxypyrimidin-4-yl substituents at positions 1, 4 and 5 respectively. It has a role as an EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor. It is a member of cyclohexanols, a member of imidazoles, a member of pyrimidines, an aromatic ether, a member of monofluorobenzenes and a secondary alcohol.

Solubility Data

Solubility (In Vitro)

DMSO: ~60 mg/mL (~162.9 mM) Water: <1 mg/mL Ethanol: ~7 mg/mL warmed (~19.0 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 3: 5% DMSO+30% PEG 300+ddH2O: 4mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7144 mL	13.5722 mL	27.1444 mL
	5 mM	0.5429 mL	2.7144 mL	5.4289 mL
	10 mM	0.2714 mL	1.3572 mL	2.7144 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.