193551-21-2 Usage
Description
SB 239063 is a member of the imidazole class, characterized by its 4-hydroxycyclohexyl, 4-fluorophenyl, and 2-methoxypyrimidin-4-yl substituents at positions 1, 4, and 5 respectively. It is a protein kinase inhibitor with neuroprotective properties, known to decrease the number of activated microglia and facilitate neurogenesis in oxygen-glucose-deprived hippocampal slice cultures.
Uses
Used in Pharmaceutical Research:
SB 239063 is used as a research tool for studying the roles of c-Jun N-terminal kinase (JNK), p38 MAP kinase, and extracellular signal-regulated protein kinase (ERK)/p42/p44 mitogen-activated protein kinase (MAPK) on the viability and apoptosis of cardiomyocytes under glutathione S-transferase (GST) inhibition. It aids in understanding the underlying mechanisms of various cellular processes and potential therapeutic targets.
Used in Neuroprotection:
SB 239063 is used as a neuroprotective agent to decrease neutrophilia, inflammatory cytokines, matrix metallopeptidase 9 (MMP-9), and fibrosis in the lung. Its neuroprotective properties make it a valuable compound in the development of treatments for neurological disorders and conditions involving neuroinflammation.
Used in Neuron-Microglia Conditioned Media (CM) Experiments:
SB 239063 is used as an experimental compound in neuron-microglia conditioned media (CM) experiments to investigate the interactions between neurons and microglia, as well as the potential therapeutic effects of the compound on these cellular interactions.
Used in Pharmacokinetics:
SB 239063 is used in pharmacokinetic studies to evaluate the absorption, distribution, metabolism, and excretion of the compound in biological systems. This information is crucial for understanding the compound's efficacy and safety profile, as well as for optimizing its therapeutic potential.
Used in Anti-Inflammatory Applications:
SB 239063 is used as an anti-inflammatory agent to decrease the number of activated microglia and reduce inflammation in the central nervous system. Its ability to modulate inflammatory responses makes it a potential candidate for the treatment of various inflammatory conditions and diseases.
Hazard
A poison by ingestion.
Biological Activity
Potent and selective p38 MAP kinase inhibitor (IC 50 = 44 nM for p38a). Displays > 220-fold selectivity over ERK, JNK1 and other kinases; ~ 3-fold more selective than SB 203580 (4-[5-(4-Fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-1H-i midazol-4-yl]pyridine and 4-[5-(4-Fluorophenyl)-2-[4-(methylsulphonyl)phenyl]-1H- imidazol-4-yl]pyridine hydrochloride
). Reduces inflammatory cytokine production and is neuroprotective following oral administration in vivo .
Biochem/physiol Actions
Potent p38 MAP kinase inhibitor. Selective for α and β. No activity against γ and δ isoforms.
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).
references
[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.
Check Digit Verification of cas no
The CAS Registry Mumber 193551-21-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,9,3,5,5 and 1 respectively; the second part has 2 digits, 2 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 193551-21:
(8*1)+(7*9)+(6*3)+(5*5)+(4*5)+(3*1)+(2*2)+(1*1)=142
142 % 10 = 2
So 193551-21-2 is a valid CAS Registry Number.
InChI:InChI=1/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/t15-,16-
193551-21-2Relevant articles and documents
Cycloalkyl substituted imidazoles
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, (2008/06/13)
1,4,5-substituted imidazole compounds and compositions for use in therapy.
Cycloalkyl substituted imidazoles
-
, (2008/06/13)
Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy.
