CU-T12-9

Selective TLR2-TLR1 agonist

Activation of TLR2-TLR1 by CU-T12-9

CU-T12-9 is a  small-molecule agonist for Toll-like receptor 2 (TLR2), that has been derived from the screening and optimization of a TLR2‑activating compound library [1, 2]. Specifically, CU-T12-9 binds and activates a single TLR2‑heterodimer, TLR2-TLR1 [1]. Furthermore, the binding site of CU-T12-9 has been suggested to be on the interface of the heterodimer, supporting its selective affinity. Importantly, even at high concentrations, CU-T12-9 maintains its selective agonistic activity, with minimal cytotoxicity.

Upon binding to the TLR2-TLR1 heterodimer, CU-T12-9 has been shown to activate NF-κB-dependent signaling, i.e. expression of TNF-α, IL-10, and iNOS [1]. Notably varying signaling outcomes (i.e. gene expression) may occur depending on which TLR2‑heterodimer is activated (InvivoGen, data not shown) and thus, TLR2 agonist selection and concentration are pivotal.

Key features of CU-T12-9:

• Exclusively activates TLR2-TLR1 heterodimer (even at high concentrations)
• Synthetic small molecule that shares no structural similarity to 'natural' TLR2 ligands (e.g. bacterial lipoproteins)
• Functionally validated with InvivoGen's HEK-Blue™ hTLR2 cell collection 

CU-T12-9 provided by InvivoGen is of the highest quality and guaranteed free of bacterial contamination. We also offer a collection of engineered HEK293-derived reporter cell lines, specifically designed for investigating  TLR1-TLR2 and/or TLR2-TLR6 signaling pathways in cellular assays.

References:

1. Cheng, K. et al. 2015. Specific activation of the TLR1-TLR2 heterodimer by small-molecule agonists. Sci Adv 1.
2. Guan, Y. et al. 2010. Identification of novel synthetic toll-like receptor 2 agonists by high throughput screening. J Biol Chem 285, 23755-23762.

Figures

CU-T12-9 triggers hTLR2 signaling in HEK‑Blue™ hTLR2 cells. The cells were incubated with increasing concentrations (0-10 µM) of CU-T12-9. After overnight incubation in HEK-Blue™ detection medium, activation of TLR2 (NF‑κB activity) was assessed by measuring SEAP activity in the supernatant. Data is shown as OD at 630 nm.

Specific activation of hTLR2-TLR1 by CU-T12-9. HEK‑Blue™ hTLR2-TLR1 and HEK-Blue™ hTLR2-TLR6 cells were incubated with increasing concentrations of CU‑T12-9 (0 - 10 µM). After overnight incubation in HEK-Blue™ detection medium, activation of TLR2-TLR1 and TLR2-TLR6 (NF‑κB activity) was assessed by measuring SEAP activity in the supernatant of each cellular assay. Data is shown as OD at 630 nm.

Specifications

Specificity: TLR2-TLR1 agonist

Working concentration: 10 nM - 10 µM

CAS number: 1821387-73-8

Molecular formula: C₁₇H₁₃F₃N₄O₂

Molecular weight: 362.31 g/mol

Solubility: 100 mM (~36 mg/ml) in DMSO

Quality control:

• Purity: ≥95% (UHPLC)
• Specific activation of the TLR2-TLR1 heterodimer by CU-T12-9 has been confirmed using HEK-Blue hTLR2 cellular assays.
• The absence of bacterial contamination (e.g. endotoxins) has been confirmed using HEK-Blue™ hTLR4 cells.

Contents

• 10 mg of CU-T12-9 (provided as a dried powder)

CU-T12-9 is shipped at room temperature.

Upon receipt, store at -20°C.

 CU-T12-9 is stable for 6 months when properly stored.

Details

Chemical structure of CU-T12-9: