CL075 (3M002)

TLR7/8 Agonist - Thiazoquinoline compound

CL075 (3M002) is a thiazoloquinolone derivative that, alike the base analog R848 (Resiquimod), induces differential TLR7 and/or TLR8  responses in human and murine immune cells.

CL075 was originally described as a human TLR8 (hTLR8) agonist because it triggers a potent NF-κB activation in hTLR8 reporter cells when compared to hTLR7 reporter cells [1].
In human peripheral blood mononuclear cells (PBMCs), CL075 induces the production of TNF-α and IL-12, and to a lesser extent IFN-α. This cytokine profile is similar to the one induced by the hTLR8 agonist ssRNA40 [1]. CL075 also induces the NF-κB-dependent production of IL-1α/β, IL-6, IL-8, MIP-1αβ, and MIP-3αβ pro-inflammatory cytokines [1]. CL075 efficiently stimulates cytokine production from monocytes and myeloid dendritic cells (DCs) among human PBMCs [1]. This compound has been used to optimize the ex vivo maturation of monocyte-derived DCs for developing DC-based anti-pathogen or anti-tumor vaccines [2]. 

Using our reporter cell lines HEK-Blue™ hTLR7, HEK-Blue™ hTLR8, HEK-Blue™ mTLR7, and HEK-Blue™ mTLR8, we established that CL075 is a TLR7/8 agonist. CL075 is ~10 times more potent for hLTR8 activation than for hTLR7. It also activates murine TLR7 (mTLR7), but not mTLR8. 

Key features of CL075:

• Agonist of hTLR7 and hTLR8 with higher potency towards hTLR8.
• Agonist of mTLR7.
• Each lot of CL075 is highly pure (>95%) and functionally tested.

References:

1. Gorden K.B. et al., 2005. Synthetic TLR agonists reveal functional differences between human TLR7 and TLR8. J. Immunol. 174(3):1259-68.
2. Spranger S. et al., 2010. Generation of Th1-polarizing dendritic cells using the TLR7/8 agonist CL075. J. Immunol. 185:738-747

Specifications

Specificity: human TLR7/8 and mouse TLR7 agonist

CAS number: 256922-53-9

Formula: C₁₃H₁₃N₃S 

Molecular weight: 243.33 g/mol

Solubility: 1 mg/ml in water

Working Concentration:

• 0.1 - 5 μg/ml CL075 for human TLR8 and mouse TLR7 in cell culture assays
• 0.5 - 5 μg/ml CL075 for human TLR7 in cell culture assays

Quality control:

• Purity: ≥95% (UHPLC)
• The biological activity of CL075 has been verified using cellular assays.
• The absence of bacterial contamination has been confirmed using HEK-Blue™ hTLR2 cells (for lipoproteins) and HEK-Blue™ hTLR4 cells (for endotoxins).

Contents

CL075 is available in two quantities:

tlrl-c75:

• 500 µg CL075
• 2 ml of sterile endotoxin-free water

tlrl-c75-5:

• 5 mg CL075
• 10 ml of sterile endotoxin-free water

CL075 is provided as a pale yellow lyophilized powder and shipped at room temperature.

Store at -20°C.

Lyophilized product is stable 1 year at -20°C when properly stored.

Resuspended CL075 should be aliquoted and stored at -20°C.

Resuspended product is stable 6 months at -20°C.

Avoid repeated freeze-thaw cycles.

Details

Chemical structure of CL075: