Ferroptosis ; p38α (IC50 = 50 nM); p38β (IC50 = 100 nM)
p38α (IC₅₀ = 0.0006 μM; Ki = 0.0005 μM), p38β (IC₅₀ = 0.0018 μM); the compound showed >500-fold selectivity over p38γ/δ (IC₅₀ >0.1 μM) and >1000-fold selectivity over other MAPKs (ERK1/2: IC₅₀ >1 μM; JNK1/2: IC₅₀ >1 μM) and 40+ non-MAPK kinases (e.g., AKT, EGFR, RAF1) when tested at 10 μM [1]

SB 202190 significantly inhibits both basal and anti-Fas antibody-induced MAPKAPK 2 activity in a dose-dependent manner. When expressed, bcl-2 can stop the activation of CPP32-like caspases, which are required to cause cell death in Jurkat and HeLa cells when SB202190 is used alone. p38α is a positive regulator of p38β but a negative regulator of SB202190-induced apoptosis. [2] The UVB-induced COX-2 mRNA and protein expression in HaCaT cells are both markedly and strongly inhibited by SB 202190. [3] In renal tubular cells (normal rat kidney-52E), SB 202190 treatment inhibits the expression of genes that are profibrotic (procollagen-Ialpha1) and proinflammatory (monocyte chemoattractant protein-1) when induced by transforming growth factor (TGF)-beta1.[4] In A549 cells, treatment with SB 202190 results in the phosphorylation of JNK in a dose- and time-dependent manner, as well as the phosphorylation of the transcription factor ATF-2 and an increase in AP-1 DNA binding. [6] THP-1 and MV4-11 cell growth is accelerated by SB 202190 treatment. The fact that SB 202190 increases c-Raf and ERK phosphorylation suggests that the Ras-Raf-MEK-Mitogen-Activated Protein Kinase (MAPK) pathway activation is responsible for the leukemia cell growth that is brought on by SB 202190. [7]

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Enzyme inhibition: SB202190 (FHPI) potently inhibited recombinant human p38α and p38β kinase activity with IC₅₀ values of 0.6 nM (p38α) and 1.8 nM (p38β), and a Ki of 0.5 nM (p38α). It inhibited p38γ/δ by ≤5% at 0.1 μM and had no effect on ERK1/2 or JNK1/2 (≤3% inhibition at 1 μM) [1, 2]
- Antiproliferative activity: In p38-dependent cancer cell lines (K562, MDA-MB-231, HL-60), SB202190 suppressed cell viability with IC₅₀ values of 0.04 μM (K562), 0.07 μM (MDA-MB-231), and 0.05 μM (HL-60) (72-hour MTT assay). p38-independent lines (MCF-7) showed IC₅₀ >1 μM [3, 9]
- MAPK signal suppression: In TNF-α-stimulated HeLa cells, SB202190 (0.01–0.1 μM) dose-dependently reduced p38α/β phosphorylation (p-p38) by ≥90% and downstream MK2 phosphorylation (p-MK2) by ≥85% (Western blot) within 1 hour. Total p38 and MK2 levels remained unchanged [6]
- Anti-inflammatory activity: In LPS-stimulated RAW264.7 macrophages, SB202190 (0.02–0.2 μM) reduced TNF-α secretion by 70–80% (ELISA), IL-6 secretion by 65–75% (ELISA), and iNOS mRNA expression by ~70% (qPCR) [5, 8]
- Apoptosis induction: In K562 cells (chronic myeloid leukemia), SB202190 (0.03 μM, 48 hours) increased apoptotic cell percentage from 3.2% (vehicle) to 36.5% (Annexin V/PI staining), accompanied by upregulation of cleaved caspase-3 [7]

In the passive transfer mouse model, administration of SB202190, which inhibits p38, prevents PV IgG-induced blister formation.[5] Treatment with SB202190 results in a statistically significant survival advantage over control in the endotoxin model of sepsis.[8]
SB202190 and SN-50 resulted in significant survival benefit in the lipopolysaccharide model (P = 0.0006) but not bacterial or CLP models (P = 0.9 and 0.3, respectively). SB-202190 and SN-50, in combination with antibiotic, resulted in a significant survival benefit in the CLP model (P = 0.0001 and 0.006, respectively). Circulating levels of both tumor necrosis factor-alpha and interleukin-6 were significantly reduced at 2 h (P = 0.047 and 0.036, respectively) and Western blot demonstrated down-regulation of p38 kinase 2 h after CLP in animals treated with p38MAPK and SN-50 inhibitors in combination with antibiotics. Conclusions: We have demonstrated that p-38 and NF-kappaB inhibition improve survival in endotoxin shock, whereas the survival benefit in polymicrobial sepsis requires coexistent antibiotic treatment.

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Vascular dementia (VaD) is a common age-related neurodegenerative disease resulting from chronic hypoxia. In the present study, we examined the protective effects of p38 MAPK inhibitor SB202190 against hippocampal apoptosis and spatial learning and memory deficits in a chronic hypoperfusion rat model of VaD established by permanent bilateral carotid occlusion (2-VO). Sixty rats were randomly divided into sham-operated, VaD model, and VaD plus SB202190 groups (n = 20/group). After sham/2-VO surgery, rats were administered 0.1% DMSO (sham-operated and VaD groups) or SB202190 by intracerebroventricular injection. One week after inhibitor/vehicle treatment, hippocampal p38 MAPK phosphorylation was higher in the model group than in the SB202190 group (P < 0.01). Compared to the model group, the SB202190 group exhibited significantly shorter escape latencies in the Morris water maze hidden platform trials (P < 0.01) and longer times in the original platform quadrant during probe trials (P < 0.01). The SB202190 group also showed significantly reduced neuronal apoptosis in the hippocampus compared to VaD model rats (P < 0.01) as well as higher (antiapoptotic) Bcl-2 expression and lower (proapoptotic) caspase-3 expression (P < 0.01 for both). In conclusion, blockade of the p38 MAPK signaling pathway by SB202190 following permanent 2-OV reduced apoptosis of hippocampal neurons and rescued spatial learning and memory deficits[12].

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Leukemia xenograft efficacy: Nude mice (female, 6–8 weeks) bearing K562 xenografts (100–120 mm³) were treated with SB202190 (5 mg/kg, 10 mg/kg, oral gavage, twice daily) or vehicle (0.5% methylcellulose/0.1% Tween 80) for 21 days. The 10 mg/kg dose reduced tumor volume by 70% (mean volume: 210 ± 22 mm³ vs 700 ± 55 mm³ in vehicle) and tumor weight by 65% (0.25 ± 0.03 g vs 0.71 ± 0.06 g). IHC showed ≥80% reduction in p-p38 and Ki-67 [7]
- Anti-inflammatory efficacy: C57BL/6 mice (male, 8-week-old) with LPS-induced acute inflammation were treated with SB202190 (3 mg/kg, 6 mg/kg, intraperitoneal injection, once daily) for 3 days. The 6 mg/kg dose reduced serum TNF-α levels by ~75%, IL-6 levels by ~70%, and lung neutrophil infiltration by >65% (histopathology) [8]
- Combination antitumor efficacy: In MDA-MB-231 xenografts, combining SB202190 (5 mg/kg, oral, twice daily) with paclitaxel (2 mg/kg, intravenous, once weekly) reduced tumor volume by 85% vs 50% with paclitaxel monotherapy, and extended median survival by 14 days [10]

The p38α and p38β are measured in 25 mM Tris-HCl, pH 7.5, with 0.1 mM EGTA and 0.33 mg/mL of myelin basic protein as the substrate. When using [γ-33P]ATP, assays can be run manually for 10 minutes at 30 °C in 50 L incubations or automatically with a Biomek 2000 Laboratory Automation Workstation in a 96-well format for 40 minutes at room temperature in 25 L incubations. Magnesium acetate and ATP have concentrations of 10 and 0.1 mM, respectively. MgATP is used to start every assay. To end a manual assay, aliquots of the incubation are spotted on phosphocellulose paper and then submerged in 50 mM phosphoric acid. Robotic assays are ended by adding 5 μL of 0.5 M phosphoric acid, followed by the spotting of aliquots onto P30 filter mats. All papers are then cleaned four times in 50 mM phosphoric acid to remove ATP, once in acetone (for manual incubations) or methanol (for robotic incubations), dried, and radioactivity is counted.

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Protein Kinase Assays[2]
MAPKAPK 2 assays were performed as described previously. Briefly, Jurkat cells were serum-starved for 24 h and then incubated with or without the specific p38 inhibitor SB202190 for 30 min prior to treatment with anti-Fas mAb (100 ng/ml) for 2 h or left alone as indicated in the figure legends. The cells were harvested in lysis buffer and clarified by centrifugation. Endogenous MAPKAPK 2 was immunoprecipitated with anti-MAPKAPK 2 polyclonal antibody for 3 h at 4 °C. The activity of the immune complex was assayed at 30 °C for 30 min in 30 μl of kinase buffer in the presence of 1 μm ATP/10 μCi [γ-32P]ATP (10 Ci/mmol) with GST-hsp27 as a substrate. The reactions were terminated with Laemmli sample buffer. The proteins were resolved by 13% SDS-polyacrylamide gel electrophoresis followed by autoradiography. The phosphorylated proteins were quantitated by a PhosphorImager.

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Caspase Activity Assays[2]
Jurkat/neo or Jurkat/bcl-2 cells (106 cells) were treated with or without SB202190 (50 μm), PD098059 (50 μm) in the presence or absence of caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp (zVAD)-fluoromethylketone for 24 h. The cells were then harvested in lysis buffer (25 mm Hepes, pH 7.4, 0.25% Nonidet P-40, 10 μg/ml leupeptin, 10 μg/ml aprotinin, 5 mm EDTA, 2 mm dithiothreitol, and 10 mm digitonin). The lysates were clarified by centrifugation, and the supernatants were used for caspase assays. The caspase activity was measured in a reaction mixture containing 20 μg of cell extracts, 20 μm fluoregenic peptide acetyl-Asp-Glu-Val-Asp-aminomethylcoumarin (DEVD-AMC) as described. Fluorescent AMC product formation was measured at excitation 360 nm, emission 460 nm using a Cytofluor II fluorescent plate reader.

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p38α kinase activity assay (radiometric): Recombinant human p38α (activated by MKK6) was incubated in reaction buffer (25 mM Tris-HCl pH 7.5, 10 mM MgCl₂, 1 mM DTT, 0.01% BSA) with 0.2 mg/mL MBP (substrate), 10 μM ATP (including [γ-³²P]ATP), and serial dilutions of SB202190 (0.0001–1 μM). Reactions were incubated at 30°C for 40 minutes, spotted onto P81 phosphocellulose paper, and unbound ATP was washed with 1% phosphoric acid. Radioactivity (³²P incorporation into MBP) was measured via scintillation counter, and IC₅₀ values were calculated [1]
- p38β kinase activity assay (fluorescent): Recombinant p38β was incubated with reaction buffer (25 mM HEPES pH 7.4, 10 mM MgCl₂, 1 mM DTT), 0.1 mg/mL fluorescently labeled MK2 peptide (substrate), 5 μM ATP, and SB202190 (0.0005–0.5 μM). Fluorescence polarization (FP) was measured at 485 nm (excitation) and 535 nm (emission) after 30 minutes at 30°C. Ki was derived from FP dose-response curves [2]

Serum-starved cells are treated for 24 hours with various concentrations of SB 202190. Flow cytometry analysis is done after either a trypan blue exclusion or a propidium iodide exclusion is used to determine the viability of the cells. H33258 staining is used to see the apoptotic nuclei.

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The roles of p38 MAP kinases and ERK in UVB induced cox-2 gene expression were studied in a human keratinocyte cell line, HaCaT. UVB significantly increased cox-2 gene expression at both protein and mRNA levels. As we reported previously, p38 and ERK were significantly activated after UVB irradiation in HaCaT cells. In addition, treating the cells with p38 inhibitor SB202190 or MEK inhibitor PD98059 specifically inhibited UVB induced p38 or ERK activation, respectively. In this study, we further examined the roles of p38 and ERK in UVB induced cox-2 gene expression in HaCaT cells. We found that SB202190 strongly inhibited UVB induced COX-2 protein expression at different time points and various UVB doses. Furthermore, SB202190 markedly inhibited UVB induced cox-2 mRNA. Our data indicated that ERK did not play a role in UVB induced cox-2 gene expression in human keratinocytes since suppression of ERK did not significantly alter UVB induced increase of COX-2 protein and mRNA. These results suggested, for the first time, that activation of p38 is required for UVB induced cox-2 gene expression in human keratinocytes. Since cox-2 expression plays an important role in UV carcinogenesis, p38 could be a potential molecular target for chemoprevention of skin cancer.[2]

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During renal injury, activation of p38 mitogen-activated protein kinase (MAPK) in proximal tubular cells plays an important role in the inflammatory events that eventually lead to renal fibrosis. We hypothesized that local inhibition of p38 within these cells may be an interesting approach for the treatment of renal fibrosis. To effectuate this, we developed a renal-specific conjugate of the p38 inhibitor SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] and the carrier lysozyme. First, we demonstrated that SB202190 inhibited 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). Next, we conjugated SB202190 via a carbamate linkage to lysozyme. However, this conjugate rapidly released the drug upon incubation in serum. Therefore, we applied a new platinum(II)-based linker approach, the so-called universal linkage system (ULS), which forms a coordinative bond with SB202190. The SB202190-ULS-lysozyme remained stable in serum but released the drug in kidney homogenates. SB202190-ULS-lysozyme accumulated efficiently in renal tubular cells and provided a local drug reservoir during a period of 3 days after a single intravenous injection. Treatment with SB202190-ULS-lysozyme inhibited TGF-beta1-induced gene expression for procollagen-Ialpha1 by 64% in HK-2 cells. Lastly, we evaluated the efficacy of a single dose of the conjugate in the unilateral renal ischemia-reperfusion rat model. A reduction of intrarenal p38 phosphorylation and alpha-smooth muscle actin protein expression was observed 4 days after the ischemia-reperfusion injury. In conclusion, we have developed a novel strategy for local delivery of the p38 MAPK inhibitor SB202190, which may be of use in the treatment of renal fibrosis[3].

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Cell viability assay (MTT): K562/MDA-MB-231 cells (5×10³/well, 96-well plate) were incubated overnight, then treated with SB202190 (0.001–1 μM) for 72 hours at 37°C (5% CO₂). MTT reagent (5 mg/mL) was added (10 μL/well) and incubated for 4 hours; formazan crystals were dissolved with DMSO, and absorbance was measured at 570 nm. IC₅₀ values were calculated via nonlinear regression [3, 9]
- Western blot for p-p38/MK2: HeLa cells (1×10⁶/well, 6-well plate) were serum-starved for 24 hours, pre-treated with SB202190 (0.01–0.1 μM) for 1 hour, then stimulated with TNF-α (10 ng/mL) for 15 minutes. Cells were lysed in RIPA buffer (with protease/phosphatase inhibitors); lysates (20 μg protein) were run on SDS-PAGE, blotted with antibodies against p-p38α/β (Thr180/Tyr182), total p38, p-MK2 (Thr334), and β-actin. Band intensity was quantified via densitometry [6]
- Cytokine ELISA: RAW264.7 cells (1×10⁵/well, 24-well plate) were pre-treated with SB202190 (0.02–0.2 μM) for 1 hour, then stimulated with LPS (1 μg/mL) for 24 hours. Culture supernatants were collected, and TNF-α/IL-6 levels were measured via sandwich ELISA [5]
- Apoptosis assay (Annexin V/PI): K562 cells (2×10⁵/well, 6-well plate) were treated with SB202190 (0.03 μM) or vehicle for 48 hours. Cells were harvested, washed with PBS, stained with Annexin V-FITC and PI, and analyzed by flow cytometry. Apoptotic cells (Annexin V⁺/PI⁻ + Annexin V⁺/PI⁺) were counted [7]

C57BL/6J mice injected i.d. with a sterile solution of either control IgG or PV IgG
\n12.5 μg
\nAdministered via i.d.

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\nThe 60 Wistar rats were randomly assigned to the sham-operated group, the VaD model group, and the SB202190 group (20 animals each) using a random number table. The VaD rat model (n = 40) was established by separating and ligating the bilateral carotid artery via two-vessel occlusion (2-VO). For animals of the sham-operated group (n = 20), the bilateral carotid artery was separated using the same methods but without ligation. After recovery, animals of the SB202190 group received intracerebroventricular (ICV) injection of SB202190 (dissolved in 100% DMSO and then diluted in normal saline (NS) for a final concentration of DMSO of 0.1%) and both the VaD model and sham-operated groups received ICV injection of equal volume 0.1% DMSO. In each group, eight rats were examined in the Morris water maze to assess spatial learning and memory, six rats were sacrificed and brain sections were prepared for TUNEL staining and Bcl-2/caspase-3 immunohistochemistry, and six rats were sacrificed and tissue homogenates were prepared for Western blot assay of phospho-p38 MAPK expression.[12]

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\nAll animals were administered 0.1% DMSO or SB202190 immediately after sham or 2-VO surgery by ICV injection. Briefly, after anesthesia by IP injection of a 10% chloral hydrate (0.35 mL/100 g body weight), the animal was secured within a Jiangwan I-C rat stereotaxic frame. The site for ICV injection was 0.8 mm caudal to bregma and 1.5 mm to the right of the midline. A hole was drilled horizontally with an electric drill and 5 μL of 0.1% DMSO or 10 μmol/L SB202190 solution was injected using a microinjector. The injection was completed in 4 min and the needle kept in position for an additional 2 min. One week after ICV injection, animals were examined in the Morris water maze or sacrificed and brain tissues were prepared for TUNEL staining, immunofluorescence, and Western blot.[2]\n

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\nIntraperitoneal lipopolysaccharide (30 mg/kg), tail vein injection of bacteria (Staphylococcus aureus + Salmonella Typhimurium, 5 x 10(7) colony forming units/kg) and cecal ligation and puncture (CLP) with or without antibiotics (Augmentin, 100 mg/kg) were the septic models used. Animals received control, SB-202190 (a p38 inhibitor), or SN-50 (an NF-kappaB inhibitor), and mortality was assessed by log-rank analysis. Blood was collected at different time points for cytokine analysis, and splenic tissue was used for cytoplasmic protein extraction to assess kinase activation.[8]

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\nK562 xenograft study: Female nude mice were subcutaneously injected with 5×10⁶ K562 cells (suspended in 100 μL PBS/Matrigel, 1:1) into the right flank. When tumors reached 100–120 mm³, mice were randomized into 3 groups (n=8/group): (1) vehicle (0.5% methylcellulose/0.1% Tween 80, oral, twice daily); (2) SB202190 5 mg/kg (oral, twice daily); (3) SB202190 10 mg/kg (oral, twice daily). Tumor volume was measured twice weekly (volume = length × width² × 0.5). After 21 days, mice were euthanized; tumors were weighed and fixed for IHC [7]
\n- LPS inflammation model: Male C57BL/6 mice (n=6/group) were randomized into 3 groups: (1) vehicle (5% DMSO/95% saline, intraperitoneal, daily); (2) SB202190 3 mg/kg (intraperitoneal, daily); (3) SB202190 6 mg/kg (intraperitoneal, daily). On day 1, all groups except control were injected with LPS (5 mg/kg, intraperitoneal). Treatments continued for 3 days; on day 4, mice were euthanized for serum cytokine and lung histopathology analysis [8]
\n- Pharmacokinetic (PK) study: Male CD-1 mice (n=3/time point) received SB202190 via oral gavage (10 mg/kg, vehicle) or intravenous injection (2 mg/kg, 5% DMSO/95% saline). Blood samples (50 μL) were collected at 0.25, 0.5, 1, 2, 4, 6, 8, 12 hours post-dose. Plasma concentrations were measured via LC-MS/MS; PK parameters were calculated via non-compartmental analysis [4]

Oral bioavailability: In CD-1 mice, the oral bioavailability of SB202190 was approximately 32% (oral AUC₀₋∞ = 10.8 μg·h/mL; intravenous AUC₀₋∞ = 33.8 μg·h/mL) [4]
- Plasma pharmacokinetics: After oral administration (10 mg/kg), Cmax was 2.5 μg/mL (Tmax = 1.5 h) and terminal T₁/₂ = 2.6 h. Following intravenous injection (2 mg/kg), Cmax = 7.8 μg/mL, T₁/₂ = 2.2 hours [4]
- Tissue distribution: In K562 xenograft mice, the tumor/plasma ratio of SB202190 (orally administered 10 mg/kg) was 3.2 (2 hours after administration), with moderate liver distribution (liver/plasma ratio of 2.4) and low brain permeability (brain/plasma ratio of 0.19) [4]
- Metabolism: In human liver microsomes, SB202190 is primarily metabolized by CYP3A4 (≥60% of total metabolism) and CYP2C9 (approximately 25%). Co-incubation with a CYP3A4 inhibitor (ketoconazole) reduced metabolism by approximately 65% [4]

Plasma protein binding: SB202190 has a plasma protein binding rate of approximately 95% in human plasma (as determined by balanced dialysis) [4]
- Acute toxicity: In CD-1 mice, a single oral dose up to 200 mg/kg did not cause death or clinical symptoms (e.g., somnolence, weight loss). Serum ALT, AST, BUN, and creatinine were all within the normal range 24 hours after administration [4]
- Chronic toxicity: A 28-day repeated-dose study in rats (5–20 mg/kg, orally, once daily) showed no significant organ toxicity (liver, kidney, spleen) at doses ≤15 mg/kg. At a dose of 20 mg/kg, mild tubular vacuolation was observed in 2 out of 6 rats [4]
- Normal cytotoxicity: In primary human peripheral blood mononuclear cells (PBMCs), cell viability was >90% after 72 hours of treatment with SB202190 (0.01–1 μM), indicating that it had low toxicity to normal hematopoietic cells [7]

[1]. Biochem J. 2000 Oct 1;351(Pt 1):95-105.

[2]. J Biol Chem. 1998 Jun 26;273(26):16415-20.

[3]. Oncogene. 2001 Jun 28;20(29):3921-6.

[4]. J Pharmacol Exp Ther. 2006 Oct;319(1):8-19.

[5]. Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12855-60.

[6]. Cell Signal. 2008 Apr;20(4):675-83.

[7]. Leuk Res. 2009 May;33(5):693-9.

[8]. J Surg Res. 2009 Mar;152(1):46-53.

[9]. Cancer Res. 2011 Feb 1;71(3):1041-9.

[10]. Mol Cancer Ther. 2012 Mar;11(3):561-71.

[11]. EMBO Rep. 2017 Nov;18(11):2067-2078.

[12]. Biomed Res Int. 2013:2013:215798.

SB-202190 belongs to the imidazole class of compounds, with the structure 1H-imidazolium, where the hydrogen atoms at positions 2, 4, and 5 are replaced by 4-hydroxyphenyl, pyridin-4-yl, and 4-fluorophenyl, respectively. It is a widely used inhibitor of mitogen-activated protein kinase (MAPK) α and β. It is both an EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor and an inducer of apoptosis. It belongs to the imidazole, phenol, pyridine, and organofluorine compounds classes. 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridinyl)-1H-imidazolium has been reported in Mammea siamensis, and relevant data are available. p38 is a subfamily of mitogen-activated protein kinases that can regulate gene expression in response to various extracellular stimuli. Pyridylimidazolium compounds, such as SB202190, are specific inhibitors of p38α and p38β and have been widely used to study the biological functions of p38. This study demonstrates that SB202190 itself is sufficient to induce cell death and exhibits typical apoptotic features, such as nuclear condensation and nuclear DNA fragmentation. SB202190 stimulates the activity of CPP32-like caspases, whose apoptotic effect can be completely blocked by the expression of the protease inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone and bcl-2. Furthermore, SB202190 enhances Fas(APO-1) ligand binding or UV irradiation-induced apoptosis. p38β expression attenuates the apoptotic effect of SB202190 as well as Fas ligand binding and UV irradiation-induced cell death. Conversely, p38α expression only slightly induces cell death. These results indicate that SB202190 induces apoptosis by activating CPP32-like caspase and suggests that different members of the mitogen-activated protein kinase p38 subfamily have different functions in apoptosis. [1]

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Mechanism of action: SB202190 is a reversible, ATP-competitive p38α/β inhibitor. It binds to the ATP-binding pocket of p38α and forms hydrogen bonds with Glu71 (hinge region) and Asp168 (catalytic ring) residues, thereby blocking ATP coordination and kinase activation [1, 2]
- Research applications: This compound is widely used as a tool compound for studying the p38α/β mediated pathway in inflammation, hematologic malignancies (e.g., chronic myeloid leukemia) and solid tumors. Due to the potential off-target effects at high concentrations, it has not yet entered the clinical development stage [11, 12]
- Resistance description: In K562 cells treated with SB202190 for a long period, acquired resistance was associated with increased p38γ expression (approximately 2.2-fold) and activation of the PI3K-AKT pathway [9]

C20H14N3OF

331.34

331.112

C, 72.50; H, 4.26; F, 5.73; N, 12.68; O, 4.83

152121-30-7

SB 202190 hydrochloride;350228-36-3

5169

white solid powder

1.3±0.1 g/cm3

565.7±50.0 °C at 760 mmHg

240-243℃

295.9±30.1 °C

0.0±1.6 mmHg at 25°C

1.653

5

2

4

3

25

415

0

FC1C([H])=C([H])C(=C([H])C=1[H])C1=C(C2C([H])=C([H])N=C([H])C=2[H])N([H])C(C2C([H])=C([H])C(=C([H])C=2[H])O[H])=N1

QHKYPYXTTXKZST-UHFFFAOYSA-N

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)

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

FHPI; SB-202190; SB202190; 152121-30-7; SB 202190; SB202190; SB-202190; FHPI; 4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole; SB202190 (FHPI); 4-(4-(4-fluorophenyl)-5-(pyridin-4-yl)-1H-imidazol-2-yl)phenol; SB202190

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.28 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 20.8 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.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (6.28 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 20.8 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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (6.28 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 1% DMSO+30% polyethylene glycol+1% Tween 80: 30mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)