| Size | Price | Stock | Qty |
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| Other Sizes |
Purity: ≥98%
SB-242235 has the potential to treat cytokine-mediated illnesses like autoimmune or inflammatory diseases because it is a potent and selective p38 MAP kinase inhibitor with an IC50 of 1.0 uM. Positive pharmacokinetic results were seen with SB-242235. However, SB-242235 showed low to moderate clearance with plasma half-lives > 4 hours in non-rodent species. Systemic plasma clearance was high in rats. The oral bioavailability was high in all preclinical species. With increasing dose, SB-242235's clearance decreased in rats and monkeys, and at high oral doses, its apparent oral bioavailability appeared to be > 100%. These non-linear elimination kinetics were also evident in the drug's apparent oral bioavailability.
| Targets |
p38 MAPK (IC50 = 1.0 μM)
SB-242235 is a selective inhibitor of p38 mitogen-activated protein kinase (p38 MAPK). In primary human chondrocytes, it inhibits IL-1β-induced p38 MAPK activation with an IC50 of approximately 1 μM [1] SB-242235 acts as a selective inhibitor of p38 MAPK, targeting the p38 MAPK signaling cascade including MAPK-activated protein kinase-2 (MAPKAPK-2) and heat shock protein 27 (HSP27) downstream of p38 MAPK [2] SB-242235 is a potent and selective p38 MAP kinase inhibitor [3] |
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| ln Vitro |
SB 242235 (0-10 μM) inhibits MAPKAP K2 activation in a dose-dependent manner with an IC50 of 1.0 μM in human chondrocytes stimulated with IL-1β[1]. SB 242235 inhibits intracellular p38 activity, MAPKAP K2 was then isolated from these cells and assessed using HSP27 as a substrate[1].
1. In bovine articular cartilage explants (BAC) treated with IL-1α, SB-242235 had no effect on proteoglycan (PG) synthesis (measured by [(35)S]-sulfate incorporation into glycosaminoglycans (GAGs)) and no effect on IL-1α-induced GAG release; however, it potently inhibited nitric oxide (NO) release from IL-1α-stimulated BAC in a dose-dependent manner with an IC50 of approximately 0.6 μM, and similar inhibitory effects on NO release were observed in primary bovine chondrocytes. The inhibitory effect on NO release in bovine chondrocytes was mediated by suppressing inducible nitric oxide synthase (iNOS) gene expression at concentrations similar to those inhibiting nitrite production. Mechanistically, the inhibition of NO release was not due to the inhibition of protein kinase C (PKC), protein kinase A (PKA) or MEK-1, and the effect on BAC was time-dependent [1] 2. In primary human chondrocytes stimulated with IL-1β, SB-242235 inhibited p38 MAP kinase activation with an IC50 of approximately 1 μM, but did not inhibit NO production or iNOS induction. In both IL-1-stimulated bovine and human chondrocyte cultures, SB-242235 inhibited PGE2 production [1] |
| ln Vivo |
SB242235 (100 mg/kg; p.o.) abolishes MAP-KAPK-2 activity and HSP27 phosphorylation[2].
SB242235 inhibits expression of the pro-inflammatory cytokines interleukin (IL)-6 and KC (murine IL-8) and COX-2[2]. In rats and monkeys, SB-242235 has been shown to have non-linear elimination kinetics, which showed up as a decrease in clearance with dose and an apparent oral bioavailability > 100% at high oral doses[3]. 1. In SKH-1 hairless mice irradiated with a single dose of UVB (360 mJ per cm²), oral administration of SB-242235 prior to UVB irradiation blocked the activation of the epidermal p38 MAPK cascade, abolished MAPKAPK-2 kinase activity and HSP27 phosphorylation, and inhibited the expression of pro-inflammatory cytokines IL-6 and KC (murine IL-8) as well as cyclooxygenase (COX)-2. UVB irradiation induced time-dependent phosphorylation of p38 MAPK, MAPKAPK-2 (with increased kinase activity) and HSP27 in murine skin, and SB-242235 abrogated these UVB-induced effects [2] |
| Enzyme Assay |
SB 242235 inhibited intracellular p38 activity, human chondrocytes were treated with different doses of SB 242235 prior to stimulation with IL-1_ for 15 min. From these cells, MAPKAP K2 was then isolated and measured using HSP27 as a substrate. With an IC50 of 1.0 uM, SB 242235 inhibited the activation of MAPKAP K2 in a dose-dependent manner.
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| Cell Assay |
1. For bovine articular cartilage explant (BAC) cultures: BAC were treated with IL-1α and SB-242235 at different concentrations. Proteoglycan synthesis was assessed by measuring [(35)S]-sulfate incorporation into glycosaminoglycans (GAGs). GAG release induced by IL-1α was quantified to evaluate the effect of SB-242235 on cartilage matrix breakdown. Nitric oxide (NO) release from IL-1α-stimulated BAC was measured, and the IC50 of SB-242235 for NO inhibition was calculated. For primary bovine chondrocytes, the effect of SB-242235 on NO release and iNOS gene expression was determined; the expression level of iNOS was analyzed to confirm the mechanism of NO inhibition. For primary human chondrocytes, IL-1β was used to stimulate p38 MAPK activation, and the inhibitory effect of SB-242235 on p38 MAPK activation (IC50 ≈1 μM) was assessed, along with measurements of NO production, iNOS induction and PGE2 levels [1]
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| Animal Protocol |
Female SKH-1 hairless mice (4–6 weeks)[2]
100 mg/kg Oral administered, 30 minutes prior to ultraviolet B (UVB) irradiation 1.SKH-1 hairless mice (female) were used in the experiment. A single dose of UVB (360 mJ per cm²) was administered to irradiate the mice’s skin. SB-242235 was administered orally to the mice prior to UVB irradiation (the specific dose and dissolution formula of SB-242235 were not reported). After irradiation, the activation of the epidermal p38 MAPK pathway (including phosphorylation of p38 MAPK, MAPKAPK-2 and HSP27), MAPKAPK-2 kinase activity, and the expression levels of IL-6, KC and COX-2 were detected at different time points [2] 3. Preclinical pharmacokinetic studies of SB-242235 were conducted in rat, dog and cynomolgus monkey (Macaca fascicularis, male). The drug was administered (the specific administration route, frequency and dissolution formula were not detailed), and plasma samples were collected at different time points to determine plasma concentrations of SB-242235. Pharmacokinetic parameters such as systemic plasma clearance, half-life and oral bioavailability were calculated. Additionally, plasma protein binding of SB-242235 was measured over a concentration range of 1000-10,000 ng ml⁻¹ [3] |
| ADME/Pharmacokinetics |
1. SB-242235 exhibited generally favorable pharmacokinetic properties in rats, dogs, and monkeys:
- Systemic plasma clearance: high in rats; low to moderate in non-rodents (dogs and monkeys) - Plasma half-life: >4 hours in non-rodents (dogs and monkeys) - Oral bioavailability: high in all tested preclinical animals (rats, dogs, and monkeys) - Elimination kinetics: non-linear in rats and monkeys, characterized by decreasing clearance with increasing dose, and apparent oral bioavailability >100% at high oral doses - Plasma protein binding: concentration-dependent, ranging from 1000 to 10,000 ng/ml⁻¹ [3] |
| References |
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| Additional Infomation |
1. SB-242235 exhibits species-specific regulation of iNOS: it inhibits iNOS gene expression and NO release in IL-1α-stimulated bovine chondrocytes/cartilage, but has no effect on IL-1β-stimulated human chondrocytes/cartilage. Conversely, SB-242235 inhibits PGE2 production in both IL-1-stimulated bovine and human chondrocyte cultures. The natural product hypomenialdisine (HYM) is a protein tyrosine kinase (PTK) inhibitor that inhibits NO production and iNOS expression in cattle and humans. These findings suggest that different pathways may regulate IL-1-induced proteoglycan degradation and NO production [1]. 2. The p38 MAPK signaling pathway can be activated by inflammatory mediators and environmental stressors such as UVB. Blocking the p38 MAPK pathway with SB-242235 may be an effective way to reduce or prevent skin damage caused by acute sun exposure [2]
3. SB-242235 (1-(4-piperidinyl)-4-(4-fluorophenyl)-5-(2-methoxy-4-pyrimidinyl)imidazolium) is a potent and selective p38 MAP kinase inhibitor that may have therapeutic effects on cytokine-mediated diseases such as autoimmune or inflammatory diseases. However, the non-linear protein binding and distribution characteristics of SB-242235 suggest that caution should be exercised when designing and interpreting its role in disease states [3] |
| Molecular Formula |
C18H17N5O3
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| Molecular Weight |
351.36
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| Exact Mass |
353.165
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| Elemental Analysis |
C, 61.53; H, 4.88; N, 19.93; O, 13.66
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| CAS # |
193746-75-7
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| Related CAS # |
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| PubChem CID |
9863367
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| Appearance |
white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
568.4±60.0 °C at 760 mmHg
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| Flash Point |
297.5±32.9 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.662
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| LogP |
3.01
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
442
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| Defined Atom Stereocenter Count |
0
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| 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])N([H])C([H])([H])C1([H])[H]
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| InChi Key |
PDTYLGXVBIWRIM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H20FN5O/c1-26-19-22-11-8-16(24-19)18-17(13-2-4-14(20)5-3-13)23-12-25(18)15-6-9-21-10-7-15/h2-5,8,11-12,15,21H,6-7,9-10H2,1H3
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| Chemical Name |
4-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]-2-methoxypyrimidine
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.07 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 (7.07 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8461 mL | 14.2304 mL | 28.4608 mL | |
| 5 mM | 0.5692 mL | 2.8461 mL | 5.6922 mL | |
| 10 mM | 0.2846 mL | 1.4230 mL | 2.8461 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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