Discovery of novel aporphine alkaloid derivative as potent TLR2 antagonist reversing macrophage polarization and neutrophil infiltration against acute inflammation

Heterocyclic-Modified Imidazoquinoline Derivatives: Selective TLR7 Agonist Regulates Tumor Microenvironment against Melanoma

“…6 Among the 10 known hTLRs, TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are mainly expressed on the cell surface, where they respond to bacterial and fungal components such as lipoprotein (TLR1, 2, 6, and 10), lipopolysaccharide (TLR4), and flagellin (TLR5). 7 By contrast, intracellular TLRs (TLR3, 7, 8, and 9) are located on the endosomal membrane and recognize nucleic acids from viruses, bacteria, and the host. 8,9 Among TLRs, TLR7 is primarily distributed in immune cells, such as myeloid dendritic cells (DCs), plasmacytoid DCs, macrophages, and B cells, mainly recognizing single-stranded RNA within the cytoplasm.…”

“…With rapid and remarkable advances in cancer immunotherapy, several diverse and effective molecular targeted strategies (e.g., small-molecule modulators, immune checkpoint inhibitors, and monoclonal antibodies) have yielded impressive breakthroughs. , The identification of novel targets and therapeutic combinations is crucial for future cancer treatment, and targeting toll-like receptors (TLRs) is a promising strategy for remodeling tumor immune composition and functionality to elicit antitumor immune responses. − Human TLRs (hTLRs 1–10) are a family of membrane pattern recognition receptors that are important in innate immunity because they recognize pathogen-associated molecular patterns and are widely expressed in immune cells . Among the 10 known hTLRs, TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are mainly expressed on the cell surface, where they respond to bacterial and fungal components such as lipoprotein (TLR1, 2, 6, and 10), lipopolysaccharide (TLR4), and flagellin (TLR5) . By contrast, intracellular TLRs (TLR3, 7, 8, and 9) are located on the endosomal membrane and recognize nucleic acids from viruses, bacteria, and the host. , …”

Small molecule modulators of immune pattern recognition receptors

“…Similar effort led to the identification of taspine and the derivative SMU-Y6. 36 Virtual screening approaches yielded several TLR2 antagonists. 37–39 For example, docking screening against a pocket located in the TLR2 TIR domain led to the identification of C29.…”