CL097
-
Cat.code:
tlrl-c97
- Documents
ABOUT
TLR7/8 Agonist - Imidazoquinoline compound
CL097 is a highly water-soluble derivative of the imidazoquinoline compound R848 (Resiquimod). Like R848, CL097 induces Toll-like receptor 7 (TLR7) and/or TLR8 responses in human and murine immune cells [1, 2]. TLR7 and TLR8 are endosomal pattern recognition receptors that play an important role in the antiviral immune response.
Mode of action
CL097 has been described as a preferential TLR7 agonist [1]. It is a strong inducer of plasmacytoid dendritic cells (pDCs) activation, representing a key therapeutic axis for cancer or other diseases [2].
Using InvivoGen's HEK-Blue™ reporter cell lines expressing human or mouse TLR7 or TLR8, we established that CL097 is a TLR7/8 agonist. CL097 is a more potent hTLR7 agonist than other TLR7/8 agonists, including CL075, and TLR7 agonists, such as Gardiquimod™, Imiquimod, and CL264. However, CL097 is a less potent hTLR8 agonist than CL075 and the TLR8 agonist TL8-506. It activates mouse TLR7 (mTLR7), but not mTLR8 (see figure).
Moreover, CL097 is able to activate TLR7- and TLR8-dependent NF-κB and IRF pathways, as assessed using our monocytic THP1-Dual™ reporter cell lines expressing two reporter genes for the NF-κB-inducible SEAP and IRF-inducible Lucia luciferase, as well as human TLR7 or TLR8 (see figure).
Key features of CL097
- Agonist of human/mouse TLR7 and human TLR8
- Higher potency towards human TLR7
- Each lot of CL097 is highly pure (≥95%) and functionally tested
References:
1. Schön M.P. & Schön M., 2008. TLR7 and TLR8 as targets in cancer therapy. Oncogene. 27:190-199.
2. Wu J. et al., 2019. pDC activation by TLR7/8 ligand CL097 compared to TLR7 ligand IMQ or TLR9 ligand CpG. J. Immunol. Res. 1749803.
All InvivoGen products are for internal research use only, and not for human or veterinary use.
SPECIFICATIONS
Specifications
C13H14N4O • HCl
0.3 - 3 µg/ml for human TLR8 and mouse TLR7 in cell culture assays, 50 ng - 3 µg/ml for human TLR7 in cell culture assays
1 mg/ml in water
0.2 µm filtration
Human/mouse TLR7 and human TLR8 activation in cellular assays
The biological activity has been verified using cellular assays., The absence of bacterial contamination has been confirmed using HEK-Blue™ hTLR2 and HEK-Blue™ hTLR4 cells.
CONTENTS
Contents
-
Product:CL097
-
Cat code:tlrl-c97
-
Quantity:500 µg
1.5 ml of sterile endotoxin-free water
Shipping & Storage
- Shipping method: Room temperature
- -20°C
- Avoid repeated freeze-thaw cycles
Storage:
Caution:
Details
TLR7 and TLR8:
TLR7 and TLR8 are endosomal pattern recognition receptors that share structural homology [1]. Both receptors are activated by single-stranded RNA (ssRNA) molecules, however, they exhibit different ligand-binding specificities and cellular expression patterns suggesting that they have nonredundant specialized roles.
TLR7 is essentially expressed by plasmacytoid dendritic cells (pDCs) but is also found in B cells and other myeloid cells [2] while TLR8 is highly expressed by myeloid cells and is absent from pDCs and B cells [2].
The endosomal distribution of TLR7 and TLR8 allows them to scan for the presence of microbial RNA in the phagocytic cargo. Their activation leads to NF-κB-, AP1-, and interferon regulatory factor (IRF)-mediated production of type I interferons (IFN-α/β) and pro-inflammatory cytokines [2].
Structural analyses have revealed that both TLR7 and TLR8 possess two binding sites (designated as Site 1 and Site 2) which do not share the same specificities.
Site 1 is highly conserved between TLR7 and TLR8 and binds nucleosides (guanosine (G) for TLR7 and uridine (U) for TLR8) or base analogs. The ligand preference for TLR7 and TLR8 is thus explained by the presence of specific residues in Site 1. Site 1 occupancy allows receptor dimerization and signaling.
Site 2 is less conserved and binds ssRNA with U(U) and U(G) motifs, respectively [3, 4]. Of note, ssRNA-binding to Site 2 is not sufficient for the formation of a signaling-competent TLR dimer but it strongly enhances the binding affinity of Site 1 [3, 4]. Thus, TLR7 and TLR8 appear to sense distinct RNA-degradation products rather than full-length ssRNAs [4].
1. Chuang T.H. & Ulevitch R.J., 2000. Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8, and hTLR9. Eur Cytokine Netw, 11:372-8.
2. Georg P. & Sander L.E., 2019. Innate sensors that regulate vaccine responses. Curr. Op. Immunol. 59:31.
3. Zhang Z. et al., 2018. Structural analyses of Toll-like receptor 7 reveal detailed RNA sequence specificity and recognition mechanism of agonistic ligands. Cell Rep. 25:3371.
4. Tanji H. et al., 2015. Toll-like receptor 8 senses degradation products of single-stranded RNA. Nat. Struct. Mol. Biol. 22:109.
Chemical structure of CL097 HCl:
DOCUMENTS
Documents
Technical Data Sheet
Validation Data Sheet
Safety Data Sheet
Certificate of analysis
Need a CoA ?