Structure of GNF351
CAS No.: 1227634-69-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
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 |
Tags: GNF351 | GNF 351 | GNF-351 | Aryl Hydrocarbon Receptor | AhR | inhibitor | 1227634-69-6 |
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H311 | Toxic in contact with skin |
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H316 | Causes mild skin irritation |
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H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
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H351 | Suspected of causing cancer |
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H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
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H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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