| Bioactivity | FICZ is a potent aryl hydrocarbon receptor (AhR) agonist with a Kd of 70 pM. | ||||||||||||
| Invitro | FICZ (0.01 nM-1 µM) alone or in combination with 50 nM MNF induces sustained CYP1A1 activity and leads to oxidative stress and activation of apoptosis via a mitochondrial-dependent pathway. In HepG2 cells, FICZ stimulates cell growth at low concentrations but inhibits cell growth at high concentrations[1]. FICZ (10,000-30,000 nM) significantly decreases CEH viability with an estimated LC50 (95% confidence intervals) of 14,000 nM. FICZ shows concentration-dependent effects on EROD activity in CEH cultures, with the mean EC50 values at 3, 8, and 24 h of 0.016 nM, 0.80 nM, and 11 nM, respectively[2]. FICZ treatment increases transcript expression of CYP1A1 in a dose-dependent manner in both the parental iPSC line and the CYP1A1 targeted clone[3]. CYP1 inhibition in the presence of FICZ results in enhanced AHR activation, suggesting that FICZ accumulates in the cell when its metabolism is blocked. CYP1 enzymes plays a role in regulating biological effects of FICZ[4].Nuclear export and degradation of the AHR protein are two additional steps in the AHR-mediated signal transduction pathway[5].Exposure to AhR agonists causes AhR-expressing cells to downregulate the receptor through the ubiquitin/proteasome degradation pathway[6]. | ||||||||||||
| Name | FICZ | ||||||||||||
| CAS | 172922-91-7 | ||||||||||||
| Formula | C19H12N2O | ||||||||||||
| Molar Mass | 284.31 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Mohammadi-Bardbori A, et al. The highly bioactive molecule and signal substance 6-formylindolo[3,2-b]carbazole (FICZ) plays bi-functional roles in cell growth and apoptosis in vitro. Arch Toxicol. 2017 Mar 13 [2]. Farmahin R, et al. Time-dependent transcriptomic and biochemical responses of 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are explained by AHR activation time. Biochem Pharmacol. 2016 Sep 1;115:134-43 [3]. Smith BW, et al. Genome Editing of the CYP1A1 Locus in iPSCs as a Platform to Map AHR Expression throughout Human Development. Stem Cells Int. 2016;2016:2574152. [4]. Wincent E, et al. Biological effects of 6-formylindolo[3,2-b]carbazole (FICZ) in vivo are enhanced by loss of CYP1A function in an Ahr2-dependent manner. Biochem Pharmacol. 2016 Jun 15;110-111:117-29. [5]. N A Davarinos, et al. Aryl Hydrocarbon Receptor Imported Into the Nucleus Following Ligand Binding Is Rapidly Degraded via the Cytosplasmic Proteasome Following Nuclear Export. J Biol Chem. 1999 Oct 1;274(40):28708-15. [6]. Riccardo Sibilano, et al. The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses. J Immunol. 2012 Jul 1;189(1):120-7. |