TL2-C29 - TLR2 signaling inhibitor

Inhibitor of TLR2 signaling

TL2-C29 is a small-molecule inhibitor of Toll-like receptor 2 (TLR2) [1]. TLR2 plays an essential role in detecting a diverse range of microbial pathogen-associated molecular patterns (PAMPs) from bacteria, fungi, parasites, and viruses [2]. TLR1 and TLR6 co-receptors are crucial for TLR2 signaling and ligand specificity. Cell surface TLR2/TLR1 and TLR2/TLR6 heterodimers bind tri- and diacylated lipoproteins, respectively [3,4]. TLR2 signaling is initiated by ligand-induced dimerization of the essential cytoplasmic TIR (Toll/interleukin-1 receptor) domains of the TLR2 heterodimers and adapter proteins. Subsequent signaling cascades lead to a pro-inflammatory response.

Mode of action:

TL2-C29 binds a pocket in the BB loop within the TLR2 TIR domain, thereby inhibiting TLR2 interaction with the MyD88 adapter molecule and downstream MAPK and NF-κB activation [1]. In human TLR2 signaling, TL2-C29 blocks both TLR2/1 and TLR2/6 pathways. In murine TLR2 signaling, TL2-C29 preferentially inhibits the TLR2/1 pathway [1, and in-house data].

More details

Key features:

• Potent inhibitor of human TLR2/1 and TLR2/6 signaling
• Potent inhibitor of murine TLR2/1 signaling
• No substantial cellular toxicity
• Inhibition of NF-κB/AP-1 signaling validated in cellular assays
• InvitroFit™ grade: each lot is highly pure (≥ 95%) and functionally tested

Learn more about TLR2 heterodimers.

References:

1. Mistry, P. et al., 2015. Inhibition of TLR2 signaling by small molecule inhibitors targeting a pocket within the TLR2 TIR domain. PNAS. 112(17):5455-5460.
2. Oliveira-Nascimento L. et al., 2012. The role of TLR2 in infection and Immunity. Front Immunol. 3(79): doi:10.3389/fimmu.2012.00079.
3. Takeuchi O. et al., 2001. Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol. 13: 933-940.
4. Takeuchi O. et al., 2002. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol. 169: 10-14.