Disease relevance of SB 202190

• SB202190 treatment enhanced FGF-2-induced neovascularization in the CAM, but the vessels displayed abnormal features indicative of hyperplasia of endothelial cells [1].
• In an effort to evaluate the impact of p38 signaling on colorectal cancer cell fate, we treated HT29, Caco2, Hct116, LS174T and SW480 cell lines with the inhibitor SB202190 specific for p38alpha/beta kinases [2].
• Consistent with this, the transcriptional activity of endogenous PR in MCF-7 breast cancer cells was preferentially inhibited by small interfering RNA for PPM1D; SB202190 failed to reverse the inhibition [3].
• Both 12(S)-HETE and AngII increased cellular hypertrophy with similar potency, and this was significantly blocked by SB202190 [4].
• Here, we demonstrate a significant reduction in rat chondrosarcoma cell proliferation following treatment with pharmacological inhibitors (SB202190 and PD169316) of p38 mitogen-activated protein (MAP) kinases [5].

High impact information on SB 202190

• MAP-kinase inhibitors (PD98059, U0216, and SB202190) significantly reduced IL-22 induction of cytokine secretion [6].
• Treatment with the p38 inhibitor SB202190 enhanced FGF-2-induced tubular morphogenesis by decreasing apoptosis, increasing DNA synthesis and cell proliferation, and enhancing the kinetics of cell differentiation including increased expression of the Notch ligand Jagged1 [1].
• Fibroblasts transfected with DN-14-3-3zeta exhibited markedly increased apoptosis in response to UVC irradiation that was blocked by pre-treatment with a p38 MAPK inhibitor, SB202190 [7].
• Further, MNK1 was activated upon stimulation of HeLa cells with 12-O-tetradecanoylphorbol-13-acetate, fetal calf serum, anisomycin, UV irradiation, tumor necrosis factor-alpha, interleukin-1beta, or osmotic shock, and the activation by these stimuli was differentially inhibited by the MEK inhibitor PD098059 or the p38 MAP kinase inhibitor SB202190 [8].
• Abrogation of rapid G(2)/M checkpoint activation by SB202190 increases the histone H2AX phosphorylation in G(2)/M cells [9].

Chemical compound and disease context of SB 202190

• MAPK inhibitors used were SB-202190 and PD-098059, whereas Clostridium botulinum C3 transferase was used as a Rho inactivator [10].
• We investigated to what extent two inhibitors, SB-202190 and SB-203580, interfere with TGFbeta-signalling in invasive MDA-MB-231 breast cancer cells [11].

Biological context of SB 202190

• Cells at high density lost their ability to synthesize MMP-2 and MMP-9 in response to fibronectin and MMP expression was restored by transfection with a dominant-negative mutant of Ha-Ras or by treatment with wortmannin, PD 98059, or SB 202190 [12].
• The p38 inhibitor SB202190 had no effect on ZBP-89-induced cell death [13].
• In contrast, inhibition of the p38MAPK pathway by SB202190 potentiated differentiation and the up-regulation of pRb and C/EBPbeta [14].
• Similarly, application of SB202190 at 50 micro m or SP600125 inhibited JNK activity, blocked transactivation, and sensitized parental cells to the four DNA-damaging drugs [15].
• However, treatment with SB203580 or SB202190 strongly enhances RA-dependent induction of cell differentiation and RA-regulated growth inhibitory responses [16].

Anatomical context of SB 202190

• Inhibition of p38 kinase by SB202190 (10 microM) blocks the rapid initiation of this checkpoint both in an immortalized cell line (mIMCD3) and in second-passage IME cells from mouse renal inner medulla. p38 inhibition does not affect exit from G(2) arrest [9].
• This last phenomenon was inhibited when hepatocytes were treated with SB 202190, which was described as a potent inhibitor of p38 and JNK activities [17].
• In contrast, a specific inhibitor of p38/HOG (SB202190) blocked PDT-induced apoptosis in LY-R cells with a lesser effect in CHO cells [18].
• SB202190 dramatically inhibited eosinophil differentiation by 71% [19].
• Pretreatment of neutrophils with MEK1 inhibitor PD98059, but not p38 MAPK inhibitor SB202190, prevented Entamoeba-induced apoptosis [20].

Associations of SB 202190 with other chemical compounds

• By contrast, neither an ERK inhibitor (PD098059) nor p38 inhibitors (SB203580 and SB202190) had an effect on Bcl-2 phosphorylation [21].
• Phosphorylation of serine 105 enhanced the transcriptional potency of GATA4, which was sensitive to U0126 (MEK1 inhibitor) but not SB202190 (p38 inhibitor) [22].
• A specific p38 MAPK inhibitor (SB202190) as well as a dominant-negative Ras mutant (Ras-N17) blocked both 12(S)-HETE and AngII effects [4].
• Conversely, inhibition of p38MAPK by SB202190 or PD169316 inhibited COX-2 expression by Ang II, but did not block COX-2 induction by EGF [23].
• However, unlike the other p38 isoforms, the kinase activity of p38delta is not blocked by the pyridinyl imidazole, 4-(4-fluorophenyl)-2-2(4-hydroxyphenyl)-5-(4-pyridyl)-imidazole (identicalto SB202190). p38delta can be activated by MKK3 and MKK6, known activators of the other isoforms [24].

Gene context of SB 202190

• The induction of COX-2 was blocked by the p38 MAP kinase inhibitor SB202190, even when added 12-16 h after stimulation with Ag when p38 MAP kinase activity had returned to near basal, but still minimally elevated, levels [25].
• In contrast, SB202190, a specific inhibitor of p38(MAPK), enhanced IL-1beta-induced LDL receptor expression, with a concomitant increase in ERK-1/2 activity [26].
• SB202190 or anti-PGE(2) monoclonal antibody compromised the stabilization of COX-2 mRNA by PGE(2) [27].
• Hence, VEGF mRNA induction is inhibited by SB202190, an inhibitor of JNK and p38/HOG kinase [28].
• EMSAs showed that SB 202190 inhibited GBS-induced AP-1 activation, but had no effect on NF-kappaB-DNA binding activity [29].

Analytical, diagnostic and therapeutic context of SB 202190

• Expression of p38beta attenuated the apoptotic effect of SB202190 and the cell death induced by Fas ligation and UV irradiation [30].
• Inhibition of p38 kinase with SB-202190 (10 micrometer) potentiated beta-AR-stimulated apoptosis as measured by flow cytometry and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining [31].
• Wortmannin, an inhibitor of PI3K, did not block the preconditioning induced stimulation of 2DG6P production, but perfusion with SB202190, an inhibitor of p38 MAP kinase, did attenuate 2DG6P accumulation (111% of initial ATP, p < 0. 05 compared with preconditioned hearts) [32].
• Dissection of individual response elements on IL-4-regulated promoter showed that C/EBP beta-mediated transcription was insensitive to SB202190 treatment in B cells whereas STAT6-mediated transcription was regulated by p38 MAPK [33].
• Interestingly, higher concentrations of SB, which drastically activated JNK, blocked megakaryocytic differentiation, and considerably increased cell death in the presence of PMA. c-DNA microarray membranes and PCR analysis allow us to identify a set of genes modulated during PMA-induced K562 cell differentiation [34].

References