TL8-506

Benzoazepine analog - TLR8 ligand

TL8-506 is a benzoazepine compound, analog of the Toll-like receptor 8 (TLR8) agonist VTX-2337 [1,2].

TL8-506 activates TLR8 more potently than the imidazoquinoline R848 (TLR7/8) and the thiazoquinolone CL075 (TLR8/7).

TL8-506 is ~50x and ~25x more potent in inducing NF-κB activation in TLR8-transfected HEK293 (HEK-Blue™ hTLR8) cells than R848 and CL075 (EC50, ~30 nM vs. ~1500 nM and 800 nM), respectively.

TL8-506 is a selective agonist of TLR8, it is ~500x more active on HEK-Blue hTLR8 than TLR7-transfected HEK293 (HEK-Blue™ hTLR7) cells (EC50, ~30 nM vs. ~15 μM).

TL8-506 has been formulated to increase its solubility in water.

References:

1. Lu H. et al., 2012. VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC. Clin Cancer Res. 18(2):499-509.
2. Elavazhagan S. et al., 2015. Granzyme B Expression Is Enhanced in Human Monocytes by TLR8 Agonists and Contributes to Antibody-Dependent Cellular Cytotoxicity. J Immunol. 194(6):2786-95.

Figures

NF-κB response of HEK-Blue™-derived cells to TL8-506. HEK-Blue™ cells expressing hTLR7, mTLR7, hTLR8, or mTLR8 cultured in HEK-Blue™ Detection reagent and stimulated with increasing concentrations of TL8-506. After 24h incubation, the NF-κB-induced SEAP activity was assessed by measuring the SEAP level in the supernatant. Data are shown as optical density (OD) at 650 nm (mean ± SEM).

Of note, HEK-Blue™ Null* comprises data from parental cell lines HEK-Blue Null1, HEK-Blue Null1-v, HEK-Blue Null2-k.

NF-κB and IRF responses of THP1-Dual™-derived cells to TL8-506. THP1-Dual™, THP1-Dual™ hTLR7 cells, THP1-Dual™ hTLR8 cells, and THP1-Dual™ hTLR7 KO-TLR8 cells were incubated for 24 hours with increasing concentrations of TL8-506. After 24h incubation, the (A) NF-κB-induced SEAP activity was assessed using QUANTI-Blue™. Data are shown as optical density (OD) at 650 nm (mean ± SEM). (B) The IRF response was assessed by measuring the activity of Lucia luciferase in the supernatant using QUANTI-Luc™. Data are shown in fold response over non-induced cells (mean ± SEM).

Specifications

Specificity: TLR8 agonist
CAS number: 1268163-15-0
Solubility: water
Formula: C20H17N3O2
Molecular weight: 331.37

Contents

• 500 µg TL8-506
• 1.5 ml sterile endotoxin-free water

TL8-506 is provided lyophilized and shipped at room temperature.

Store at -20°C.

Details

Chemical structure of TL8-506: