Disease relevance of 53153-43-8

• Effects of pyrazole and 3-amino-1,2,4-triazole on the metabolism and toxicity of dimethylnitrosamine in the rat [1].
• There was increased survival of CA1 neurons in rats treated with the COX2-selective inhibitor SC58125 [1-[(4-methylsulfonyl) phenyl]-3-trifluoro-methyl-5-[(4-fluoro)phenyl] pyrazole] before or after global ischemia compared with vehicle controls [2].
• The biological effects of pyrazole were measured either as toxicity to the rats or as mutations to Salmonella TA 92 [3].
• We report the discovery of a class of pyrazole-based compounds that are potent inhibitors of the dihydroorotate dehydrogenase of Helicobacter pylori but that do not inhibit the cognate enzymes from Gram-positive bacteria or humans [4].
• YM-58483, a pyrazole derivative, inhibited an anti-CD3 mAb-induced sustained Ca(2+) influx in acute T cell leukemia, Jurkat cells [5].

Psychiatry related information on 53153-43-8

• In addition to the disturbances in food and water consumption, pyrazole also caused a decrease in locomotor activity which was only partly due to the starvation [6].

High impact information on 53153-43-8

• Pyrazole-induced thyroid necrosis: a distinct organ lesion [7].
• One oral dose of pyrazole caused necrosis of rat thyroid follicular epithelial cells but spared the parafollicular (C) cells and the parathyroid glands [7].
• Further, although both inhibitors delayed the incorporation of radioactivity from [14C]DMN into hepatic subcellular organelles, pyrazole was significantly more effective than was 3-AT [1].
• Through detailed structural analysis of the interaction of the initially discovered pyrazole carboxylic ester scaffold with PDE4D using X-ray crystallography, we identified three sites of chemical substitution and designed small selective libraries of scaffold derivatives with modifications at these sites [8].
• A 4,000-fold increase in the potency of this PDE4 inhibitor was achieved after only two rounds of chemical synthesis and the structural analysis of seven pyrazole derivatives bound to PDE4B or PDE4D, revealing the robustness of this approach for identifying new inhibitors that can be further developed into drug candidates [8].

Chemical compound and disease context of 53153-43-8

• The correlation between the in vivo toxicity and in vitro mutagenicity of dimethylnitrosamine and the activity of dimethylnitrosamine demethylase I (DMND I) after pyrazole treatment of rats was studied [3].
• SB203580, a p38 MAPK inhibitor, and PD98059, an ERK inhibitor, but not wortmannin a phosphatidylinositol 3-kinase (PI3K) inhibitor, prevented AA toxicity in pyrazole hepatocytes and E47 cells [9].
• Hepatocytes from pyrazole-treated rats, with high levels of CYP2E1, were more sensitive to Fe + AA toxicity than were saline control hepatocytyes [10].
• Antiviral activity of Win 41258-3, a pyrazole compound, against herpes simplex virus in mouse genital infection and in guinea pig skin infection [11].
• The tryptophan synthase alpha 2 beta 2 complex from Escherichia coli has been found to catalyze the beta-replacement reaction of L-serine with indazole, an indole analog which has a nitrogen atom at the 2-position (pyrazole ring) [12].

Biological context of 53153-43-8

• CMZ protected against the pyrazole enhanced LPS liver injury and oxidative stress [13].
• Pyrazole, a potent inhibitor of ADH, inhibited MAM metabolism as well as liver DNA methylation in the ADH(+) strain; however similar inhibition of these processes also occurred in the ADH(-) strain [14].
• When microsomes from the pyrazole-treated animals were used in the mutagenesis assay, there was a linear correlation between DMND I activity and the number of histidine-revertant colonies [3].
• DNA fragmentation and caspase-8 and -3 activities were more elevated in the Pyr/Jo2 group compared with Jo2 alone [15].
• In contrast to transcriptional activation during development, induction of P450j by various agents such as pyrazole, 4-methylpyrazole, and acetone might be due to post-transcriptional events [16].

Anatomical context of 53153-43-8

• Similar results were found in hepatocytes from pyrazole-treated rats with high levels of CYP2E1 [17].
• One of the seven MAbs tested, 1-91-3, inhibited enzyme activity of acetone-, pyrazole-, or methylpyrazole-induced microsomes by 54, 47, and 48%, respectively [18].
• Potent inhibition of Ca2+ release-activated Ca2+ channels and T-lymphocyte activation by the pyrazole derivative BTP2 [19].
• Kupffer cells were the only macrophages showing significant MCP-1 release, which was markedly reduced by E2 or propyl pyrazole triol in wild-type and in ER-beta-/- mice [20].
• A pyrazole derivative potently inhibits lymphocyte Ca2+ influx and cytokine production by facilitating transient receptor potential melastatin 4 channel activity [21].

Associations of 53153-43-8 with other chemical compounds

• The "IKCa1-pharmacophore" consists of a (2-halogenophenyl)diphenylmethane moiety substituted by an unsubstituted polar pi-electron-rich heterocycle (pyrazole or tetrazole) or a -CN group, whereas cytochrome P450 inhibition absolutely requires the imidazole ring [22].
• Glutathione and activities of catalase and Cu-Zn superoxide dismutase were decreased in the Pyr/Jo2 group [15].
• LPS-induced oxidative stress was also enhanced by pyrazole as indicated by increases in 4-hydroxy-2-nonenal and 3-nitrotyrosine adduct formation [13].
• The enzyme activity was not affected by pyrazole, an inhibitor of alcohol dehydrogenase and sodium azide, an inhibitor of catalase [23].
• When ethanol treatment was combined with 4-methyl pyrazole so as to block ethanol oxidation, the ethanol-induced increase in proline uptake was significantly decreased to levels similar to that seen in controls [24].

Gene context of 53153-43-8

• HO-1 induction was observed in the livers of chronic alcohol-fed mice or pyrazole-treated rats, conditions known to elevate CYP2E1 levels [25].
• To test these hypotheses, female B57BL/J6 mice received E2 (50 microg/25 g) or vehicle after trauma-hemorrhage and female 129 Sve ER-beta-/- transgenic mice and ovariectomized wild-type mice received E2 or ER-alpha agonist propyl pyrazole triol (50 microg/25 g) after trauma-hemorrhage [20].
• We also show that a specific hepatotoxic inducer of the Cyp2a5 gene, pyrazole, increases the cytoplasmic levels of hnRNP A1 in vivo [26].
• Kinetic characterization of novel pyrazole TGF-beta receptor I kinase inhibitors and their blockade of the epithelial-mesenchymal transition [27].
• PCR amplification of a 1 kb region in Cyp2a-4/5-mRNA-derived cDNA, followed by cutting at the diagnostic PstI site, showed that most of the steady-state mRNA consisted of Cyp2a-5, which is also the form most affected by pyrazole [28].

Analytical, diagnostic and therapeutic context of 53153-43-8

• CYP2E1-knockout mice exhibited only minor liver injury after treatment with pyrazole/LPS, but wild-type mice exhibited severe liver injury [13].
• LPS-induced liver injury was enhanced by pyrazole, as indicated by pathological changes and increases in ALT and AST, and positive TUNEL staining [13].
• Human liver alcohol dehydrogenase (ADH, EC 1.1.1.1) was purified by double ternary complex affinity chromatography on Sepharose-4-(3-[N-6 aminocaproyl]aminopropyl) pyrazole [29].
• Similar studies in obese fasted subjects pretreated with an intravenous infusion of insulin (1.0 U/hr. for eight hours) before receiving Pyrazole resulted in a 65 plus or minus 5 per cent decrease in plasma Beta-OHB [30].
• Similar results were observed in co-culture with primary hepatocytes from saline- or pyrazole-treated (with high levels of CYP2E1) rats [31].

References