AhR Ligand - FICZ

Tryptophan-derived agonist of AhR

FICZ (6-Formylindolo[3,2-b]carbazole) is a highly potent ligand of the cytosolic aryl hydrocarbon receptor (AhR) transcription factor.
The presence of FICZ-derived metabolites in human urine points FICZ to be an endogenous AhR agonist, but which requires diet-derived tryptophan (Trp) amino acid [1]. FICZ synthesis results from Trp conversion upon UV-dependent photo-oxidation or H₂O₂-mediated oxidative stress [2,3].

InvivoGen's FICZ is a high-quality product (>95% purity) and is guaranteed free of bacterial contamination. Each lot of FICZ is functionally tested in cellular assays using HepG2-Lucia™ AhR and HT29-Lucia™ AhR reporter cells.

CH-223191, an AhR antagonist is also available.

Read our review on AhR's key role in the intestinal microbiota and immunity.

References:

1. Wincent E. et al., 2009. The suggested physiologic aryl hydrocarbon receptor activator and cytochrome P4501 substrate 6-formylindolo[3,2-b]carbazole is present in humans. J. Biol. Chem. 284:2690-96.
2. Rannug A. et al., 1987. Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances. J. Biol. Chem. 262:15422-27.
3. Smirnova A. et al., 2018. Evidence for new light-independent pathways for generation of the endogenous aryl hydorcarbon receptor agonist FICZ. Chem. Res. Toxicol. 29:75-86.

Figures

FICZ induces a dose-dependent response in HepG2-Lucia™ Ahr and HT29-Lucia™ Ahr cells.
The cells were incubated with increasing concentrations of FICZ. After overnight incubation, the AhR activation
was assessed by determining Lucia luciferase activity in the supernatant using QUANTI-Luc™ 4 Lucia/Gaussia.
Data are expressed as fold responses, as compared to non-induced cells.

Specifications

CAS number: 172922-91-7

Synonym: 6-Formylindolo[3,2-b]carbazole

Solubility: 10 mg/ml (37.17 mM) in DMSO

Working concentration: 50 ng/ml (0.18 µM) to 5 μg/ml (18 μM) for cell culture assays

Formula: C₁₉H₁₂N₂O

Molecular weight: 284.31 g/mol

Quality control:

• Purity ≥ 95% (UHPLC).
• The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK‑Blue™ TLR4 cells.
• The biological activity has been validated using cellular assays.

Contents

• 1 mg FICZ
   

FICZ is shipped at room temperature.

Store at -20°C.

Details

FICZ chemical structure

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcriptional factor able to sense a wide range of structurally different exogenous and endogenous molecules.

AhR ligands vary in their structure, and their binding affinity can significantly differ between mouse and human AhR [1].  AhR agonists have been found to arise from xenobiotics such as pollutants, and indoles mainly derived from tryptophan metabolism occurring in the stomach and in the gut, as well as in other organs upon photo-oxidation or oxidative stress. The prototypic high-affinity AhR agonist, the xenobiotic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), displays a 10-fold higher affinity for mouse AhR compared to human AhR. Conversely, dietary-derived indole metabolites have a better affinity for human AhR; a possible consequence of evolution [1-3].

References:

1. Lamas B. et al., 2018. Aryl hydrocarbon receptor and intestinal immunity. Mucosal Immunol. 11(4):1024-38.
2. Murray I.A. et al., 2017. Ligand activation of the Ah receptor contributes to gastrointestinal homeostasis. Curr. Opin. Toxicol. 2:15-23.
3. Hubbard T.D. et al., 2015. Indole and tryptophan metabolism: endogenous and dietary routes to Ah receptor activation. Drug Metab. Dispos. 43:1522-35.