VAF347 is a cell permeable and highly affinity aryl hydrocarbon receptor (AhR) agonist and induces AhR signaling. VAF347 inhibits the development of CD14+CD11b+ monocytes from granulo-monocytic (GM stage) precursors. VAF347 has anti-inflammatory effects[1].
VAF347 (0.01-20 μM; 48-72 hours; HL-60 cells) treatment enhances retinoic acid-induced cell cycle arrest[1].VAF347 (20 μM; 48 hours; HL-60 cells) treatment augments retinoic acid-induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47phox. Several interactions of partners in the signalsome appear to be enhanced: Fgr interaction with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn[1].VAF347 inhibits IL-4+ GM-CSF induced IL-6 production in MM1 cells with an IC50 of ~5 nM[2]. Cell Cycle Analysis[1] Cell Line: HL-60 cells
In wild-type mice, VAF347 treatment leads to a strong reduction of total serum IgE levels compared with vehicle-treated animals. IL-5 levels in the bronchoalveolar fluid are inhibited to a comparable degree. AhR-deficient mice are resistant to the VAF347's ability to block allergic lung inflammation in vivo[2].
[1]. Ibabao CN, et al. The AhR agonist VAF347 augments retinoic acid-induced differentiation in leukemia cells. FEBS Open Bio. 2015 Apr 8;5:308-18. [2]. B Paige Lawrence, et al. 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.