Targeting Toll-like receptors: emerging therapeutics?
There is a growing interest in the targeting of Toll-like receptors (TLRs) for the prevention and treatment of cancer, rheumatoid arthritis, inflammatory bowel disease and systemic lupus erythematosus (SLE). Several new compounds are now undergoing preclinical and clinical evaluation, with a particular focus on TLR7 and TLR9 activators as adjuvants in infection and cancer, and inhibitors of TLR2, TLR4, TLR7 and TLR9 for the treatment of sepsis and inflammatory diseases. Here, we focus on TLRs that hold the most promise for drug discovery research, highlighting agents that are in the discovery phase and in clinical trials,and on the emerging new aspects of TLR-mediated signalling - such as control by ubiquitination and regulation by microRNAs - that might offer further possibilities of therapeutic manipulation.
Hennessy
Elizabeth J
EJ
Trinity College Dublin,School of Biochemistry and Immunology, Dublin 2, Ireland.
Parker
Andrew E
AE
O'Neill
Luke A J
LA
D000818:Animals; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects
D035683:MicroRNAs; D051193:Toll-Like Receptors