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Chemical Structure| 1227634-69-6 Chemical Structure| 1227634-69-6

Structure of GNF351
CAS No.: 1227634-69-6

Chemical Structure| 1227634-69-6

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GNF351 is a full aryl hydrocarbon receptor (AHR) antagonist. GNF351 competes with a photoaffinity AHR ligand for binding to the AHR with IC50 of 62 nM.

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Product Details of GNF351

CAS No. :1227634-69-6
Formula : C24H25N7
M.W : 411.50
SMILES Code : CC1=CN=CC(C2=NC(NCCC3=CNC4=C3C=CC=C4)=C5N=CN(C(C)C)C5=N2)=C1
MDL No. :MFCD23726597
InChI Key :ABXIUYMKZDZUDC-UHFFFAOYSA-N
Pubchem ID :46216378

Safety of GNF351

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
Primary HFLS-RA cells 100 nM 1 h Inhibits IL1B-induced inflammatory signaling Ann Rheum Dis. 2013 Oct;72(10):1708-16
HN13 cells 100 nM 48 hours Reduction in MMP9 secretion Mol Cancer Res. 2012 Oct;10(10):1369-79
Primary esophageal epithelial cells 2 μM 30 minutes GNF-351 pretreatment was used to evaluate the role of the AHR signaling pathway in PPI-induced transcriptional responses. Results showed that GNF-351 inhibited PPI-induced expression of CYP1A1 and HMOX1 genes, indicating that the AHR signaling pathway plays a partial role in PPI-mediated transcriptional responses. J Allergy Clin Immunol. 2021 May;147(5):1924-1935
EPC2 cells 2 μM 30 minutes GNF-351, a high-affinity antagonist of the AHR signaling pathway, was used to block the transcriptional responses mediated by PPIs through the AHR signaling pathway. Results showed that GNF-351 pretreatment significantly inhibited the PPI-induced expression of CYP1A1 and CYP1B1 genes but had no effect on the induction of MT1H gene. J Allergy Clin Immunol. 2021 May;147(5):1924-1935
human bone-derived mesenchymal stem cells (hBMSCs) 100 nM 17 days To evaluate the impact of TCDD on osteogenic differentiation of hBMSCs. Results showed that 10 nM TCDD consistently attenuated alkaline phosphatase (ALP) activity and matrix mineralization, downregulated osteogenic markers (ALP, OPN, and IBSP), and upregulated FGF9 and FGF18 expression. Coexposure with the AhR antagonist GNF351 blocked TCDD-mediated attenuation of matrix mineralization and partially or fully rescued expression of genes associated with osteogenic regulation. Toxicol Sci. 2019 Jan 1;167(1):145-156
Primary FLS 500 nM 1 hours AHR activation in TCDD-treated COS-1 cells leads to enhanced transcriptional activity of VEGF-A, EREG, and AREG promoters J Pharmacol Exp Ther. 2014 Feb;348(2):236-45
HN2095 cells 100 nM 12 hours Reduction in IL6 transcription and CYP1A1 activity Mol Cancer Res. 2012 Oct;10(10):1369-79
HN30 cells 100 nM 24 hours Reduction in IL6 transcription and CYP1A1 activity Mol Cancer Res. 2012 Oct;10(10):1369-79
K4IM cells 500 nM 1 h Inhibits IL1B-induced inflammatory signaling Ann Rheum Dis. 2013 Oct;72(10):1708-16
Primary HFLS-N cells 100 nM 1 h Inhibits IL1B-induced inflammatory signaling Ann Rheum Dis. 2013 Oct;72(10):1708-16
Mouse intestinal microsomes 100 μM 30 minutes Identification of GNF-351 metabolites, including two oxidized GNF-351 and one tri-demethylated GNF-351 Br J Pharmacol. 2014 Apr;171(7):1735-46
Human intestinal microsomes 100 μM 30 minutes Identification of GNF-351 metabolites, including two oxidized GNF-351 and one tri-demethylated GNF-351 Br J Pharmacol. 2014 Apr;171(7):1735-46
Mouse liver microsomes 100 μM 30 minutes Identification of GNF-351 metabolites, including two oxidized GNF-351 and one tri-demethylated GNF-351 Br J Pharmacol. 2014 Apr;171(7):1735-46
Human liver microsomes 100 μM 30 minutes Identification of GNF-351 metabolites, including two oxidized GNF-351 and one tri-demethylated GNF-351 Br J Pharmacol. 2014 Apr;171(7):1735-46
normal human epidermal keratinocytes 100 nM 24 hours GNF351 inhibited the TCDD-mediated RNA and transcriptional increases J Invest Dermatol. 2023 Oct;143(10):1964-1972. e4
Primary FLS cells from RA patients 500 nM 4 hours GNF351 significantly inhibits IL1B-mediated enhanced expression of EREG, AREG, VEGF-A, and FGF-2 mRNA J Pharmacol Exp Ther. 2014 Feb;348(2):236-45
Primary FLS cells from healthy individuals 500 nM 4 hours GNF351 significantly inhibits IL1B-mediated enhanced expression of EREG, AREG, VEGF-A, and FGF-2 mRNA J Pharmacol Exp Ther. 2014 Feb;348(2):236-45
Huh7 cells 1 μM 1-hour pretreatment followed by 6 hours Evaluate the inhibitory effect of GNF351 on acute-phase gene expression, results showed GNF351 failed to inhibit SAA1 expression J Pharmacol Exp Ther. 2011 Jul;338(1):318-27
H1L1.1.1c2 cells 100 nM 4 hours Evaluate the antagonistic effect of GNF351 on mouse AHR, results showed GNF351 could antagonize TCDD-induced AHR activity J Pharmacol Exp Ther. 2011 Jul;338(1):318-27
HepG2 40/6 cells 100 nM to 10 μM 4 hours Evaluate the agonist activity of GNF351 on AHR, results showed no significant agonist activity was observed in the tested concentration range J Pharmacol Exp Ther. 2011 Jul;338(1):318-27

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mouse C57BL/6J mice Oral 5 mg/kg Single dose, observed for 24 hours Evaluation of GNF-351 absorption and metabolism, results showed GNF-351 was not detected in serum and mostly found in feces Br J Pharmacol. 2014 Apr;171(7):1735-46

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.43mL

0.49mL

0.24mL

12.15mL

2.43mL

1.22mL

24.30mL

4.86mL

2.43mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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