TLR-8 ligands Library

ChemDiv’s library of small molecule ligands targeting toll-like receptor type-8 contains 597 compounds.

Toll-Like Receptor 8 is a protein expressed in the endosomes of certain cells, notably immune cells. It is part of the leukocyte pattern recognition receptors (PRRs) subfamily, which are an essential link in the mechanism of identifying various pathogens. TLR8 is found in various immune cells, including monocytes, macrophages, T cells, and predominantly in myeloid dendritic cells. TLR8, along with TLR7, plays a crucial role in recognizing single-stranded RNA (ssRNA) that is rich in purines. This recognition is vital in mounting an immune response against pathogens that are detected in the endosome, such as viruses and bacteria. For example, TLR8 can identify ssRNAs from influenza and HIV, both of which are viruses that use this type of genetic material.

TLR8 signals through the MyD88/MAL pathway. This pathway involves the recruitment of the IL-1 receptor-associated kinase-4 (IRAK-4), which subsequently leads to the production of cytokines and interferons (IFNs). This production is mediated through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and IFN regulatory factors. These molecules are crucial in the immune response, as they help orchestrate the defense against pathogens. In response to proinflammatory cytokine signaling, the transcription of TLR7 and TLR8 is induced via NF-kB. This means that when the body detects inflammation, it increases the production of these receptors to enhance its ability to detect and respond to pathogens [1].

Given its crucial role in the immune response, dysregulation of TLR8 can lead to the onset of diseases. TLR8 overexpression can lead to excessive immune responses, potentially contributing to autoimmune diseases, while its underactivity might result in inadequate immune responses, leading to increased susceptibility to infections. TLR8's pivotal role in the immune response makes it a promising target for drug development. Medications that modulate TLR8 activity could potentially be used as therapies for a range of diseases. For instance, TLR8 agonists might boost the immune response against pathogens or cancer cells, while antagonists (inhibitors) could help in conditions where the immune system is overactive, such as in autoimmune diseases.

Our TLR8 ligand library is a collection of molecules designed to interact with Toll-Like Receptor 8, which is crucial for drug discovery. They enable targeted drug development by providing a range of compounds that specifically interact with TLR8, aiding in understanding the receptor's mechanism and role in immune responses. This library accelerates the drug discovery process by offering pre-identified ligands for screening, facilitating the search for potential therapeutics, including both inhibitors and activators, depending on therapeutic needs. It also allows for comparative studies and the potential development of combination therapies. Additionally, the library can assist in identifying biomarkers for diseases, streamlining the development of more effective and specific treatments, particularly for conditions where immune response modulation is essential.

References

[1] D. J. Dowling, “Recent Advances in the Discovery and Delivery of TLR7/8 Agonists as Vaccine Adjuvants,” ImmunoHorizons, vol. 2, no. 6, pp. 185–197, 2018, doi: 10.4049/immunohorizons.1700063.