| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
VAF347 acts as a high-affinity ligand for the aryl hydrocarbon receptor (AhR). Upon binding, it triggers AhR translocation to the nucleus, heterodimerization with ARNT (aryl hydrocarbon receptor nuclear translocator), and binding to xenobiotic response elements (XREs) in DNA. This activates transcription of AhR target genes, including CYP1A1, CYP1B1, and IL-22. The compound's immunomodulatory effects are mediated through AhR-dependent pathways.
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| ln Vitro |
Treatment with VAF347 (0.01–20 μM; 48–72 hours; HL-60 cells) improves the cell life cycle triggered by retinoic acid [1]. Treatment with VAF347 (20 μM; 48 h; HL-60 cells) improves the cell cycle initiated by retinoic acid[1]. expression of AhR, Lyn, Vav1, c-Cbl, and p47phox that is stimulated by acid. The MM1 cells' IL-4+ GM-CSF-induced IL-6 production is inhibited by Fgr with c-Cbl, CD38, and pS259c-Raf and AhR with c-Cbl and VAF347; the IC50 is roughly 5 nM[2]. Several responses appear to be amplified in the signalosome.
In vitro, VAF347 activates AhR with high potency. It induces CYP1A1 mRNA expression in human HepG2 cells with an EC50 of approximately 1-5 nM. The compound inhibits IL-6 production in LPS-stimulated human peripheral blood mononuclear cells (PBMCs) with an IC50 of 2.5 nM. It also promotes the differentiation of regulatory T cells (Tregs) in vitro at concentrations of 1-10 nM, enhancing FoxP3 expression. |
| ln Vivo |
Total serum IgE levels in wild-type mice treated with VAF347 were significantly lower than in animals given vehicle therapy. Significantly less IL-5 was present in the mutant alveolar fluid. VAF347 can cause allergic lung inflammation in vivo, although AhR-deficient animals are not susceptible to this effect [2].
In vivo, VAF347 has demonstrated therapeutic efficacy in animal models of autoimmune diseases. In a mouse model of experimental autoimmune encephalomyelitis (EAE), oral administration of VAF347 (1-10 mg/kg/day) significantly reduced disease severity and spinal cord inflammation. In a rat model of collagen-induced arthritis, VAF347 (5 mg/kg/day, p.o.) reduced paw swelling and joint destruction. The compound also showed efficacy in a murine model of allergic airway inflammation. |
| Enzyme Assay |
The in vitro AhR binding assay is performed using competitive ligand binding. Human AhR protein (full-length or LBD domain) is incubated with 10 nM [³H]-TCDD and increasing concentrations of VAF347 (0.1 nM to 10 µM) at 25°C for 2 hours in binding buffer (50 mM HEPES, 100 mM NaCl, 1 mM DTT, 0.1% CHAPS). Unbound ligand is separated using a hydroxyapatite column, and radioactivity is counted. IC50 and Ki values are calculated from displacement curves.
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| Cell Assay |
Cell cycle analysis [1]
Cell Types: HL-60 Cell Tested Concentrations: 10 nM, 100 nM, 1 μM, 10 μM, 20 μM Incubation Duration: 48 hrs (hours) or 72 hrs (hours) Experimental Results: Enhanced retinoic acid-induced G1/0 cell cycle Stagnation. Western Blot Analysis[1] Cell Types: HL-60 Cell Tested Concentrations: 20 μM Incubation Duration: 48 hrs (hours) Experimental Results: Enhanced retinoic acid-induced expression of AhR, Lyn, Vav1 and c-Cbl, and p47phox. For in vitro cell-based AhR activation assays, HepG2 cells stably transfected with a CYP1A1-luciferase reporter construct are seeded in 96-well plates. Cells are treated with VAF347 at concentrations of 0.01-1000 nM for 24 hours at 37°C in a 5% CO₂ incubator. After incubation, the cells are lysed and luciferase activity is measured. The EC50 is calculated by non-linear regression. Cytotoxicity is assessed by a parallel MTT assay. |
| Animal Protocol |
For in vivo EAE studies, female C57BL/6 mice are immunized subcutaneously with MOG₃₅₋₅₅ peptide (100 µg) emulsified in complete Freund's adjuvant. Pertussis toxin is injected intraperitoneally on days 0 and 2. Starting on day 0, VAF347 is administered orally at doses of 1, 3, or 10 mg/kg daily for 21 days. Clinical scores are recorded daily. On day 21, spinal cords are collected for histopathological analysis (H&E and Luxol fast blue staining) and cytokine profiling.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies in Sprague-Dawley rats following oral administration (10 mg/kg) show that VAF347 reaches peak plasma concentrations (Cmax) of 2.5 µg/mL at 2 hours post-dose. The oral bioavailability is approximately 45% and the plasma half-life is 6.5 hours. The compound is highly bound to plasma proteins (~98%). It is metabolized primarily by CYP1A1 and CYP3A4 enzymes. Elimination is mainly via the biliary route with some renal excretion.
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| Toxicity/Toxicokinetics |
In preclinical toxicity studies, VAF347 shows a favorable safety profile. The oral LD50 in rats is >1000 mg/kg. At therapeutic doses (1-10 mg/kg), no significant hepatotoxicity or nephrotoxicity is observed. At high doses (≥100 mg/kg), elevation of liver enzymes (ALT/AST) and mild hepatomegaly are noted. No mutagenic potential is detected in the Ames test.
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| References |
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| Additional Infomation |
Nonsteroidal anti-inflammatory drugs
VAF347 is a white to pale yellow solid with a molecular weight of 369.4 g/mol. It is soluble in DMSO and ethanol but poorly soluble in water. The compound is a valuable research tool for studying AhR-mediated immunomodulation. It has been investigated as a potential therapeutic agent for autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. Clinical trials have not been reported. |
| Molecular Formula |
C₁₇H₁₁CLF₃N₃
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| Molecular Weight |
349.74
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| Exact Mass |
349.059
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| CAS # |
574759-62-9
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| PubChem CID |
10172275
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| Appearance |
White to off-white solid powder
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| LogP |
5.632
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
24
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| Complexity |
399
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC(=C1)Cl)C2=NC(=NC=C2)NC3=CC=C(C=C3)C(F)(F)F
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| InChi Key |
XTKUZTBZRIJTFR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H11ClF3N3/c18-13-3-1-2-11(10-13)15-8-9-22-16(24-15)23-14-6-4-12(5-7-14)17(19,20)21/h1-10H,(H,22,23,24)
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| Chemical Name |
4-(3-chlorophenyl)-N-[4-(trifluoromethyl)phenyl]pyrimidin-2-amine
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| Synonyms |
VAF 347 VAF-347
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~31.25 mg/mL (~89.35 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (5.95 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8593 mL | 14.2963 mL | 28.5927 mL | |
| 5 mM | 0.5719 mL | 2.8593 mL | 5.7185 mL | |
| 10 mM | 0.2859 mL | 1.4296 mL | 2.8593 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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