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Purity: ≥98%
CU-CPT17e is a multi-TLR (Toll-like receptor) agonist that activates TLR3, TLR8, and TLR9 with immunomodulatory activities. Therapies based on activation of multiple Toll-like receptors (TLRs) may offer superior therapeutic profiles than that of single TLR activation. CU-CPT17e was identified from a cell-based high-throughput screening of a small-molecule library based on TLR3-mediated NF-κB activation. Biochemical studies demonstrated that CU-CPT17e could induce a strong immune response via the production of various cytokines in human monocytic THP-1 cells. Furthermore, CU-CPT17e inhibited the proliferation of HeLa cancer cells by triggering apoptosis and arresting the cell cycle at the S phase. These results showcase potential therapeutic applications of CU-CPT17e in both vaccine adjuvants and anticancer therapies based on multi-TLR activation.
| Targets |
Toll-like Receptor 3 (TLR3) [1]
- Toll-like Receptor 8 (TLR8) [1] - Toll-like Receptor 9 (TLR9)[1] |
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| ln Vitro |
CU-CPT17e showed substantial NF-κB activation in TLR3, TLR8 and TLR9 HEK293 cells, with EC50 values of 4.80±0.73, 13.5±0.58 and 5.66±0.17 μM, respectively. CU-CPT17e dramatically boosted NF-κB activity, boosting NF-κB activation by 13.9±0.9 times, with an EC50 value of 4.8±0.7 μM. CU-CPT17e suppresses the proliferation of HeLa carcinoma cells by activating apoptosis and stopping the cell cycle in S phase. The induction of apoptosis by CU-CPT17e in HeLa cells was examined. HeLa cells were grown in increasing doses of CU-CPT17e or poly I:C or blank control (DMSO) for 24 h. Treatment with CU-CPT17e at varied concentrations (10 to 40 μM) for 24 hours resulted in a 10% to 17% rise in the apoptotic cell population, which was more effective than poly I:C at 5 μg/mL. These data imply that the antiproliferative activity of CU-CPT17e on HeLa cells may be due to its ability to directly trigger apoptosis [1].
1. Proinflammatory activity in THP-1 cells: CU-CPT17e induced a strong immune response in human monocytic THP-1 cells by promoting the production of various cytokines (specific types of cytokines not specified in the literature). This activity was mediated through the activation of multiple TLRs (TLR3, TLR8, TLR9) [1] 2. Anticancer activity in HeLa cells: CU-CPT17e effectively inhibited the proliferation of HeLa cancer cells. Mechanistically, it triggered apoptosis of HeLa cells and arrested the cell cycle at the S phase, thereby suppressing cancer cell growth [1] |
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| ln Vivo |
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| Cell Assay |
1. Cytokine production assay in THP-1 cells:
- Cell seeding: Human monocytic THP-1 cells were seeded into appropriate culture plates at a suitable density and incubated in a 37°C, 5% CO₂ incubator to allow adaptation [1] - Drug treatment: CU-CPT17e was added to the cell culture at different concentrations, and the cells were further incubated for a specified period (not detailed in the literature) to induce cytokine production [1] - Cytokine detection: After incubation, the cell culture supernatant was collected, and the levels of various cytokines were measured using relevant detection methods (not specified in the literature) to evaluate the proinflammatory activity of CU-CPT17e [1] 2. Antiproliferation, apoptosis, and cell cycle assay in HeLa cells: - Cell seeding: HeLa cancer cells were seeded into culture plates at a predetermined density and cultured overnight to ensure cell adhesion [1] - Drug treatment: CU-CPT17e was added to the HeLa cell culture at different concentrations, and the cells were incubated for a certain duration (not detailed in the literature) [1] - Proliferation detection: The proliferation status of HeLa cells was assessed using appropriate methods (not specified in the literature) to determine the antiproliferative effect of CU-CPT17e [1] - Apoptosis detection: Apoptosis of HeLa cells was detected through relevant assays (not detailed in the literature) to confirm the apoptotic-inducing activity of CU-CPT17e [1] - Cell cycle analysis: HeLa cells were processed and analyzed using cell cycle detection techniques (not specified in the literature) to verify that CU-CPT17e arrests the cell cycle at the S phase [1] |
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| Animal Protocol |
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| References | |||
| Additional Infomation |
1. CU-CPT17e is the first small molecule discovered to be able to simultaneously activate TLR3, TLR8 and TLR9[1]
2. Therapies based on multiple TLR activations are considered to have better therapeutic effects than single TLR activation, which is the theoretical basis for the development of CU-CPT17e[1] 3. CU-CPT17e was discovered through cell-based high-throughput screening of a small molecule library targeting TLR3-mediated NF-κB activation, followed by structural optimization and reverse screening for other TLRs[1] 4. Due to its pro-inflammatory activity, CU-CPT17e has shown potential therapeutic value in vaccine adjuvants and anticancer therapies (due to its anti-proliferative and apoptosis-inducing activities)[1] |
| Molecular Formula |
C27H24N2O8
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| Molecular Weight |
504.488067626953
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| Exact Mass |
504.153
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| CAS # |
2109805-75-4
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| Related CAS # |
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| PubChem CID |
132585194
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
37
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| Complexity |
804
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C2C=C(C(=CC=2C=CC21CCOCC2)OCC1C=CC(=CC=1)[N+](=O)[O-])OCC1C=CC(=CC=1)[N+](=O)[O-]
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| InChi Key |
LHTNFHWDTHQECR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H24N2O8/c30-28(31)22-5-1-19(2-6-22)17-35-25-15-21-9-10-27(11-13-34-14-12-27)37-24(21)16-26(25)36-18-20-3-7-23(8-4-20)29(32)33/h1-10,15-16H,11-14,17-18H2
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| Chemical Name |
6,7-bis[(4-nitrophenyl)methoxy]spiro[chromene-2,4'-oxane]
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9822 mL | 9.9110 mL | 19.8220 mL | |
| 5 mM | 0.3964 mL | 1.9822 mL | 3.9644 mL | |
| 10 mM | 0.1982 mL | 0.9911 mL | 1.9822 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.
 J Med Chem.2017 Jun 22;60(12):5029-5044.
TLR8 inhibitors suppress the proinflammatory cytokine production in multiple human primary cells derived from different patients. |
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Crystal structure of the TLR8/CU-CPT8m complex.
CU-CPT8m potently and selectively inhibited TLR8. |
 Proposed antagonistic mechanism of CU-CPT compounds (top) and schematic representation of domain arrangement in each TLR8 forms (bottom). TLR8 inhibitors consistently recognize an allosteric pocket on the protein-protein interface, stabilizing the inactive TLR8 dimer |
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