| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg |
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| Targets |
CU-115 targets Toll-like receptor 8 (TLR8), a member of the TLR family that plays a critical role in the innate immune response by recognizing single-stranded RNA (ssRNA) from viruses and bacteria. TLR8 is primarily expressed in human monocytes, macrophages, and dendritic cells. Upon activation, it triggers a signaling cascade that leads to the production of pro-inflammatory cytokines such as TNF-α and IL-1β. By acting as a potent and selective antagonist, CU-115 binds to TLR8 and inhibits this signaling pathway, thereby reducing the inflammatory response. It shows high selectivity for TLR8 over TLR7 (IC50 > 50 μM for TLR7 compared to 1.04 μM for TLR8).
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| ln Vitro |
Human embryonic kidney (HEK) 293 cells expressing human Toll-like receptor (hTLR) genes and inducible secretory embryonic alkaline phosphatase (SEAP) reporter genes were compared with CU -115 combined for 16 hours in endosomal and non-endosomal TLR specificity experiments. Therefore, at low doses (0.5 μM), CU-115 shows action against TLR7 and TLR8. Among HEK-293 TLR1/2, TLR2/6, TLR3, and TLR4 cells, CU-115 did not affect the NF-kB inhibition produced by Pam2CSK4, Pam3CSK4, Poly(I:C), LPS, R848, or Flic. Between 10 and 25 percent is the amount that CU-115 inhibits TLR9 signaling at 1, 5, and 20 µM. CU-115 (5–20 µM) suppresses the increase in type I IFN transcriptional activity caused by the ssRNA nucleic acid ligand 3p–hpRNA or G3–YSD in a luciferase reporter test. In Hek293 TLR7 and TLR8 cells, CU-115 (0.5, 1.0, 5, and 20 µM; 16 hours) is lethal at 100 µM and benign at low concentrations (0.5 and 20 µM). Additionally, at low concentrations (0.5 and 20 μM), CU-115 was harmless; but, at 100 μM, it partially harmed THP Dual cells. TNF-α upregulation/inhibition in human THP-1 cells was assessed using the enzyme-linked immunosorbent assay (ELISA) (hTHP-1). TNF-α production in hTHP1 triggered by R848 (1 µg/ml) is eliminated by CU-115 (5–20 µM). In hTHP-1 cells, it also suppresses the expression of IL-1β. These findings suggest that TLR8 and TLR7 signaling pathways are inhibited by CU-115.
CU-115 demonstrates potent in vitro activity as a TLR8 antagonist. It inhibits the production of TNF-α and IL-1β activated by the TLR7/8 agonist R-848 in THP-1 cells. In HEK293 TLR8 cells, CU-115 (5-20 µM) suppresses the increase in type I IFN transcriptional activity caused by ssRNA nucleic acid ligands 3p-hpRNA or G3-YSD in a luciferase reporter test. At concentrations of 1, 5, and 20 µM, it inhibits TLR9 signaling by 10-25%. Importantly, CU-115 does not affect NF-κB induction in HEK293 cells expressing TLR1/2, TLR2/6, TLR3, or TLR4 when stimulated with their respective ligands. |
| ln Vivo |
In vivo data for CU-115 is limited in publicly available sources, as it is primarily used as a research tool for in vitro studies. However, given its potent and selective inhibition of TLR8, it is a valuable compound for studying the role of TLR8 in various disease models. Its potential to modulate inflammatory responses suggests it could be useful in preclinical models of autoimmune and inflammatory diseases. Specific in vivo studies, including dosing regimens and animal models, are not detailed in the available literature but may be found in primary research publications.
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| Enzyme Assay |
The inhibitory activity of CU-115 is assessed using in vitro cell-based reporter assays. HEK293 cells expressing human TLR8 are transfected with a NF-κB-dependent luciferase reporter construct. Cells are treated with varying concentrations of CU-115 and then stimulated with a TLR8 agonist such as R-848 or a specific ssRNA ligand. The luciferase activity is measured, and the IC50 is calculated from the dose-response curve. The compound's selectivity for TLR8 over TLR7 and other TLRs is confirmed by testing it in similar assays using cells expressing these receptors.
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| Cell Assay |
The cellular activity of CU-115 is evaluated in human monocytic cell lines, such as THP-1 cells. Cells are pre-incubated with varying concentrations of CU-115 and then stimulated with the TLR7/8 agonist R-848. The production of pro-inflammatory cytokines, including TNF-α and IL-1β, is measured in the cell culture supernatant by ELISA. The compound's ability to inhibit cytokine production is quantified, and the IC50 is calculated. This assay confirms the compound's functional activity as a TLR8 antagonist in a physiologically relevant cell type.
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| Animal Protocol |
In animal studies, CU-115 would typically be administered to mice via intraperitoneal (i.p.) or oral administration to study the effects of TLR8 inhibition in vivo. In models of inflammation or autoimmune disease, the compound could be given to assess its effect on disease severity and inflammatory markers. However, specific in vivo protocols for CU-115 are not detailed in the available literature. Researchers would need to establish appropriate dosing regimens based on the compound's pharmacokinetic properties.
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| ADME/Pharmacokinetics |
CU-115 is a small molecule with a molecular weight of 569.21 and a formula of C21H11F7INO2. It is soluble in DMSO (45 mg/mL) and is typically stored as a powder at -20°C or in solution at -80°C. Its chemical name is N-(4-(3,5-bis(trifluoromethyl)phenoxy)phenyl)-2-fluoro-6-iodobenzamide. Detailed pharmacokinetic parameters, such as half-life and bioavailability, are not extensively documented in publicly available sources.
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| Toxicity/Toxicokinetics |
Toxicology data for CU-115 is limited, as it is a research compound not intended for human therapeutic use. Its safety profile has not been established in formal toxicology studies. However, its use in cell-based assays at effective concentrations suggests it is tolerated in those contexts. As with all research chemicals, standard laboratory safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
CU-115 (CAS: 2471982-20-2) is a valuable and widely used chemical probe for studying TLR8 biology. Its high selectivity for TLR8 over TLR7 and other TLRs makes it a key tool for dissecting the specific functions of TLR8 in innate immunity and inflammation. The compound was discovered and characterized in a study on novel small molecule dual inhibitors targeting Toll-like receptors 7 and 8. It is available from various commercial suppliers for research purposes and is cited in the scientific literature as a reference compound for TLR8 studies.
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| Molecular Formula |
C21H11F7INO2
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|---|---|
| Molecular Weight |
569.211
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| Exact Mass |
568.972
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| CAS # |
2471982-20-2
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| PubChem CID |
154734323
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| Appearance |
White to off-white solid powder
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| Density |
1.7±0.1 g/cm3
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| Boiling Point |
427.3±45.0 °C at 760 mmHg
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| Flash Point |
212.2±28.7 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.577
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| LogP |
5.16
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
615
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=C(C(=C1)I)C(=O)NC2=CC=C(C=C2)OC3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)F
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| InChi Key |
QYSLCRYVUJORPX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H11F7INO2/c22-16-2-1-3-17(29)18(16)19(31)30-13-4-6-14(7-5-13)32-15-9-11(20(23,24)25)8-12(10-15)21(26,27)28/h1-10H,(H,30,31)
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| Chemical Name |
N-[4-[3,5-bis(trifluoromethyl)phenoxy]phenyl]-2-fluoro-6-iodobenzamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~175.68 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7568 mL | 8.7841 mL | 17.5682 mL | |
| 5 mM | 0.3514 mL | 1.7568 mL | 3.5136 mL | |
| 10 mM | 0.1757 mL | 0.8784 mL | 1.7568 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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