VAF347 (VAF-347) is a novel and potent aryl hydrocarbon receptor (AhR) agonist which is cell permeable and has highly affinity against aryl hydrocarbon receptor (AhR). It has anti-inflammatory effects by inducing AhR signaling and nhibiting the development of CD14+CD11b+ monocytes from granulo-monocytic (GM stage) precursors.
Physicochemical Properties
| Molecular Formula | C₁₇H₁₁CLF₃N₃ |
| Molecular Weight | 349.74 |
| Exact Mass | 349.059 |
| CAS # | 574759-62-9 |
| PubChem CID | 10172275 |
| Appearance | White to off-white solid powder |
| LogP | 5.632 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 24 |
| Complexity | 399 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | XTKUZTBZRIJTFR-UHFFFAOYSA-N |
| 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) |
| Chemical Name | 4-(3-chlorophenyl)-N-[4-(trifluoromethyl)phenyl]pyrimidin-2-amine |
| Synonyms | VAF 347 VAF-347 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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. |
| 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]. |
| 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. |
| References |
[1]. The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells. FEBS Open Bio. 2015 Apr 8;5:308-18. [2]. Activation of the aryl hydrocarbon receptor is essential for mediating the anti-inflammatory effects of a novel low-molecular-weight compound. Blood. 2008 Aug 15;112(4):1158-65. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~31.25 mg/mL (~89.35 mM) |
| 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 |