| Description | Resiquimod (R848) is an imidazoquinoline amine and Toll-like receptor (TLR) agonist with potential immune response modifying activity. Resiquimod exerts its effect through the TLR signaling pathway by binding to and activating TLR7 and 8 mainly on dendritic cells, macrophages, and B-lymphocytes. This induces the nuclear translocation of the transcription activator NF-kB as well as activation of other transcription factors. This may lead to an increase in mRNA levels and subsequent production of cytokines, especially interferon-alpha (INF-a) and other cytokines, thereby enhancing T-helper 1 (Th1) immune responses. In addition, topical application of resiquimod appears to activate Langerhans' cells, leading to an enhanced activation of T-lymphocytes. |
| In vitro | Resiquimod induces the differentiation of myeloid-derived suppressor cells into dendritic cells and macrophages and may improve cancer immunotherapy by reducing immunosuppressive MDSCs. Resiquimod activates immune cells and induces proliferation of wild-type splenocytes via the Toll-like receptor 7 (TLR7)-MyD88-dependent signaling pathway [1]. Resiquimod also modulates dendritic cells to augment HIV-1- and cytomegalovirus-specific T cell responses [2]. |
| In vivo | In wild-type mice, Resiquimod (50 nmol, i.p.) promotes increased serum concentrations of TNF-α, IFN-α, and IL-12, while neither MyD88-deficient mice nor TLR7-deficient mice show an increase in these cytokines [1]. In a murine model of allergic asthma, Resiquimod (i.n., 20 μg/mouse) reduces allergen-induced airway reactivity and inflammation via the reduction in Nrf2 signaling. |
| Cell experiments | Resiquimod is dissolved in DMSO. For inhibition of lysosomal acidification, cells are incubated with 10?μM CQ for 1?h before Resiquimod (R848) treatment. After treatment, 20?μL of 5?mg/mL MTT is added to the plate. The plate is incubated at 22°C for 4?h, and 200?μL dimethyl sulfoxide is added to the plate to dissolve the reduced formazan. The plate is then read at 490?nm with a microplate reader. To determine the effect of Myd88 inhibition on R848-induced cell proliferation, the Myd88 inhibitor Pepinh-MYD and the control peptide Pepinh-Control are added to PBL at the concentration of 50?μM, and the plate is incubated at 22°C for 6?h. After incubation, the cells are treated with R848 and subjected to MTT assay as above. To determine the effect of NF-κB inactivation on R848-induced cell proliferation, BAY-11-7082, an irreversible inhibitor of IκB-α phosphorylation, is added to the cells at the concentration of 1?μM, and the plate is incubated at 22°C for 1?h. After incubation, the cells are treated with R848 and subjected to MTT assay as earlier. All experiments are performed three times. |
| Animal experiments | Animal Models: Wild-type mice,TLR7-deficient mice,and MyD88-deficient mice. Formulation: saline. Dosages: 50 nmol. Administration: i.p. |
| Synonyms | R848, 雷西莫特, S28463 |
| molecular weight | 314.38 |
| Molecular formula | C17H22N4O2 |
| CAS | 144875-48-9 |
| Storage | store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | H2O: < 1 mg/mL (insoluble or slightly soluble) DMSO: 55 mg/mL (174.95 mM) Ethanol: 20 mg/mL (63.6 mM) |
| References | 1. Hemmi H, et al. Nat Immunol. 2002, 3(2), 196-200. 2. Loré K, et al. J Immunol. 2003, 171(8), 4320-4328. 3. Lee M, et al. Arch Pharm Res. 2014, 37(9), 1234-1240. 4. Nadeem A, et al. Int J Biochem Cell Biol. 2016, 73, 53-62. 6. Zhou ZX, et al. Immune effects of R848: evidences that suggest an essential role of TLR7/8-induced, Myd88- and NF-κB-dependent signaling in the antiviral immunity of Japanese flounder (Paralichthys olivaceus). Dev Comp Immunol. 2015 Mar;49(1):113-20. 7. Gao Y, Wang K, Wang P, et al. A novel network pharmacology strategy to decode mechanism of Lang Chuang Wan in treating systemic lupus erythematosus[J]. Frontiers in Pharmacology . 2020, 11. |
| Citations | 1. Gao Y, Wang K, Wang P, et al A novel network pharmacology strategy to decode mechanism of Lang Chuang Wan in treating systemic lupus erythematosus. Frontiers in Pharmacology. 2020, 11. 2. Li J X, Shu N, Zhang Y J, et al.Self-Assembled Nanoparticles from the Amphiphilic Prodrug of Resiquimod for Improved Cancer Immunotherapy.ACS Applied Materials & Interfaces.2024 |