R848

R848 is an imidazoquinoline and agonist of Toll-like receptors (TLRs) 7 and 8. It mimics the pathogen-associated molecular patterns that activate immune cells through TLR7 and TLR8, and thereby acts as an immune-response modifier. It demonstrates potent anti-tumor and anti-viral properties (IC₅₀ = 4.2 μM; Seganish et al.) which appear to be mediated predominantly through the induction of cytokines, including interferon (IFN)-α and interleukin (IL)-12 due to stimulation of monocytes, macrophages, and dendritic cells (Bernstein et al.; Hattermann et al.; Nian et al.).

IMMUNOLOGY

• Triggers activation of human B cells, including activation of c-Jun kinase, p38 and NF-κB transcription factors (Bishop et al.).
• Induces proliferation and cytokine production by human CD4+ T cells (Caron et al.).
• Primes human neutrophils for leukotriene B4, prostaglandin E2, and platelet-activating factor biosynthesis (Hattermann et al.).
• Suppresses HIV-1 replication in monocytes (Nian et al.).
• Induces expression of IL-12 and IFN-É£ in mouse and human peripheral blood cell cultures (Wagner et al.).

DIFFERENTIATION

• Targets osteoclast precursors and inhibits their differentiation into osteoclasts via TLR7 (Miyamoto et al.).
• Induces myeloid differentiation of CD34+ hematopoietic progenitor cells, including upregulated expression of cytokines (IL-1β, TNF-α, IL-6, GM-CSF) and CD11c surface marker (Sioud et al.).