Aryl hydrocarbon receptor (AhR) are transcription factors that regulate gene expression. Specifically, AHR proteins contain several domains that are critical for their function. They are members of the basic helix loop helix/per Arnt sim (bHLH/PAS) family. Besides, AHR combines several exogenous ligands, such as natural plant flavonoids, polyphenols and indoles, as well as synthetic polycyclic aromatic hydrocarbons and dioxins. Moreover, AHR is a normally inactive cytoplasmic transcription factor that binds to several chaperone proteins. Recently, it has been found that AhR is activated (or inactivated) by many endogenous indole derivatives, such as guanosine. In addition to regulating metabolic enzymes, AhR can also regulate immunity, maintain stem cells and differentiated cells. Furthermore, It is well known that AHR has a variety of antitumor and homeostatic regulatory effects in vivo. And AHR acts in a ligand agonist or antagonist specific manner. VAF347 is a highly affinity AhR agonist.

VAF347 is a highly affinity aryl hydrocarbon receptor (AhR) agonist.

How does VAF347 work on the target? Let’s study it together. In the beginning, VAF347 is a cell-permeable and highly affinity AhR agonist and induces AhR signaling. Meanwhile, VAF347 inhibits the development of CD14⁺CD11b⁺ monocytes from granulo-monocytic (GM stage) precursors. Nonetheless, VAF347 has anti-inflammatory effects.

In the second place, VAF347 treatment enhances retinoic acid-induced HL-60 cells cycle arrest with 0.01-20 μM of 48-72 hours. Importantly, VAF347 treatment augments retinoic acid-induced expression of AhR, Lyn, Vav1, and c-Cbl as well as p47phox. Particularly, VAF347 enhanced Several interactions of partners in the signalosome. It includes Fgr interaction with c-Cbl, CD38, and with pS259c-Raf and AhR interaction with c-Cbl and Lyn.

All in all, VAF347 is a cell-permeable and highly affinity AhR agonist.

References:

Ibabao CN, et al. FEBS Open Bio. 2015 Apr 8;5:308-18.