产品号 #73782_C
免疫调节剂;TLR7和TLR8激动剂
总览
R848是一种咪唑喹啉类药物，是Toll样受体 (TLR) 7和8的激动剂。它模拟病原体相关的分子模式，通过TLR7和TLR8激活免疫细胞，从而可作为免疫反应调节剂。它具有强大的抗肿瘤和抗病毒特性（IC₅₀= 4.2 μM；Seganish et al.），可能主要通过刺激单核细胞、巨噬细胞和树突状细胞分泌细胞因子来进行调控，包括干扰素 (IFN) - α和白介素 (IL) -12（Bernstein et al.; Hattermann et al.; Nian et al.）。
免疫学
·触发人B细胞的激活，包括激活c-Jun激酶、p38和NF-κB转录因子（Bishop et al.）。
·诱导人CD4+ T细胞增殖和细胞因子产生（Caron et al.）。
·启动人中性粒细胞进行白三烯B4、前列腺素E2和血小板活化因子的生物合成（Hattermann et al.）。
·抑制HIV-1在单核细胞中的复制（Nian et al.）。·诱导小鼠和人外周血培养物中IL-12和IFN- ɣ的表达（Wagner et al.）。
分化
·靶向破骨细胞前体并通过TLR7抑制其分化为破骨细胞（Miyamoto et al.）。
·诱导CD34+造血祖细胞的髓系分化，包括上调细胞因子（IL-1β、TNF-α、IL-6、GM-CSF）和CD11c表面标志物的表达（Sioud et al.）。
细胞类型
B 细胞，粒细胞及其亚群，造血干/祖细胞，单核细胞，成骨细胞，T 细胞，T 细胞，CD4+
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
应用
激活，分化
研究领域
免疫
CAS 编号
144875-48-9
化学式
C₁₇H₂₂N₄O₂
纯度
≥98%
通路
先天免疫（固有免疫）
靶点
TLR
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Applications
This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.
Resources and Publications
Publications (10)
Discovery and Structure Enabled Synthesis of 2,6-Diaminopyrimidin-4-one IRAK4 Inhibitors. ACS medicinal chemistry letters 2015 AUG
Abstract
We report the identification and synthesis of a series of aminopyrimidin-4-one IRAK4 inhibitors. Through high throughput screening, an aminopyrimidine hit was identified and modified via structure enabled design to generate a new, potent, and kinase selective pyrimidin-4-one chemotype. This chemotype is exemplified by compound 16, which has potent IRAK4 inhibition activity (IC50 = 27 nM) and excellent kinase selectivity (textgreater100-fold against 99% of 111 tested kinases), and compound 31, which displays potent IRAK4 activity (IC50 = 93 nM) and good rat bioavailability (F = 42%).
R848, a toll-like receptor 7 agonist, inhibits osteoclast differentiation but not survival or bone-resorbing function of mature osteoclasts. Cytotechnology 2012 MAY
Abstract
R848, also known as resiquimod, acts as a ligand for toll-like receptor 7 (TLR7) and activates immune cells. In this study, we examined the effects of R848 on differentiation, survival, and bone-resorbing function of osteoclasts. R848 inhibited osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) and human peripheral blood-derived monocytes induced by receptor activator of NF-κB ligand in a dose-dependent manner. In addition, it inhibited mouse osteoclast differentiation induced in cocultures of bone marrow cells and osteoblasts in the presence of dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. However, R848 did not affect the survival or bone-resorbing activity of mouse mature osteoclasts. R848 also upregulated the mRNA expression levels of interleukin (IL)-6, IL-12, interferon (IFN)-γ, and inducible nitric oxide synthase in mouse BMMs expressing TLR7. IFN-β was consistently expressed in the BMMs and addition of neutralizing antibodies against IFN-β to the cultures partially recovered osteoclast differentiation inhibited by R848. These results suggest that R848 targets osteoclast precursors and inhibits their differentiation into osteoclasts via TLR7.
R-848 triggers the expression of TLR7/8 and suppresses HIV replication in monocytes. BMC infectious diseases 2012 JAN
Abstract
BACKGROUND Toll-like receptors (TLR) 7 and 8 are important in single-stranded viral RNA recognition and may play a role in HIV infection and disease progression. We analyzed TLR7/8 expression and signaling in monocytes from HIV-infected and uninfected subjects to investigate a pathway with new potential for the suppression of HIV replication. METHODS Eighty-one HIV-infected and uninfected subjects from Liaoning and Henan provinces in China participated in this study. Monocytes were isolated from subjects' peripheral blood mononuclear cells by magnetic bead selection. TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR. R-848 (resiquimod) was used as a ligand for TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-α secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848. RESULTS We found that expression of TLR7/8 mRNA in peripheral blood monocytes decreased with disease progression. TLR7 expression was decreased with stimulation with the TLR7/8 agonist, R-848, in vitro, whereas TLR8 expression was unaffected. Following R-848 stimulation, monocytes from HIV-infected subjects produced significantly less TNF-α than those from uninfected subjects, but trended towards greater production of IL-12 than stimulated monocytes from uninfected subjects. R-848 stimulation also suppressed HIV replication in cultured monocytes. CONCLUSIONS Our study provides evidence that the TLR7 and TLR8 triggering can suppress HIV replication in monocytes and lead to postpone HIV disease progression, thereby offering novel targets for immunomodulatory therapy.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 144875-48-9 |
| Chemical Formula | C₁₇H₂₂N₄O₂ |
| Purity | ≥ 98% |
| Target | TLR |
| Pathway | Innate Immunity |
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