For research use only. Not for therapeutic Use.
<p style=/line-height:25px/>CH-223191 is a ligand-selective antagonist of the Ah (Dioxin) receptor.<br>IC50 value:<br>Target: AhR antagonist<br>in vitro: CH-223191 preferentially inhibits the ability of some classes of AhR agonists (2,3,7,8-tetrachlorodibenzo-p-dioxin and related HAHs), but not others (PAHs, flavonoids, or indirubin), to bind to and/or activate the AhR and AhR signal transduction [1]. CH-223191 potently inhibits TCDD-induced AhR-dependent transcription. In addition, CH-223191 blocked the binding of TCDD to AhR and inhibited TCDD-mediated nuclear translocation and DNA binding of AhR [2].</p>
| Catalog Number | I003050 |
| CAS Number | 301326-22-7 |
| Synonyms | 2-methyl-N-[2-methyl-4-[(2-methylphenyl)diazenyl]phenyl]pyrazole-3-carboxamide |
| Molecular Formula | C₁₉H₁₉N₅O |
| Purity | ≥95% |
| Target | Aryl Hydrocarbon Receptor |
| Solubility | DMSO: ≥ 35 mg/mL |
| Storage | Store at +4C |
| InChI | InChI=1S/C19H19N5O/c1-13-6-4-5-7-17(13)23-22-15-8-9-16(14(2)12-15)21-19(25)18-10-11-20-24(18)3/h4-12H,1-3H3,(H,21,25) |
| InChIKey | LKTNEXPODAWWFM-UHFFFAOYSA-N |
| SMILES | CC1=CC=CC=C1N=NC2=CC(=C(C=C2)NC(=O)C3=CC=NN3C)C |
| Reference | 1:Mol Pharmacol. 2006 Jun;69(6):1871-8. Epub 2006 Mar 15. Novel compound 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191) prevents 2,3,7,8-TCDD-induced toxicity by antagonizing the aryl hydrocarbon receptor.Kim SH,Henry EC,Kim DK,Kim YH,Shin KJ,Han MS,Lee TG,Kang JK,Gasiewicz TA,Ryu SH,Suh PG, PMID: 16540597 DOI: 10.1124/mol.105.021832 </br><span>Abstract:</span> 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental pollutant with many toxic effects, including endocrine disruption, reproductive dysfunction, immunotoxicity, liver damage, and cancer. These are mediated by TCDD binding to and activating the aryl hydrocarbon receptor (AhR), a basic helix-loop-helix transcription factor. In this regard, targeting the AhR using novel small molecule inhibitors is an attractive strategy for the development of potential preventive agents. In this study, by screening a chemical library composed of approximately 10,000 compounds, we identified a novel compound, 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191), that potently inhibits TCDD-induced AhR-dependent transcription. In addition, CH-223191 blocked the binding of TCDD to AhR and inhibited TCDD-mediated nuclear translocation and DNA binding of AhR. These inhibitory effects of CH-223191 prevented the expression of cytochrome P450 enzymes, target genes of the AhR. Unlike many known antagonists of AhR, CH-223191 did not have detectable AhR agonist-like activity or estrogenic potency, suggesting that CH-223191 is a specific antagonist of AhR. It is noteworthy that CH-223191 potently prevented TCDD-elicited cytochrome P450 induction, liver toxicity, and wasting syndrome in mice. Taken together, these results demonstrate that this novel compound, CH-223191, may be a useful agent for the study of AhR-mediated signal transduction and the prevention of TCDD-associated pathology. |
