A concise review on advances in development of small molecule anti-inflammatory therapeutics emphasising AMPK: An emerging target

Abstract

Inflammatory diseases are complex, multi-factorial outcomes of evolutionarily conserved tissue repair processes. For decades, non-steroidal anti-inflammatory drugs and cyclooxygenase inhibitors, the primary drugs of choice for the management of inflammatory diseases, addressed individual targets in the arachidonic acid pathway. Unsatisfactory safety and efficacy profiles of the above have necessitated the development of multi-target agents to treat complex inflammatory diseases. Current anti-inflammatory therapies still fall short of clinical needs and the clinical trial results of multi-target therapeutics are anticipated. Additionally, new drug targets are emerging with improved understanding of molecular mechanisms controlling the pathophysiology of inflammation. This review presents an outline of small molecules and drug targets in anti-inflammatory therapeutics with a summary of a newly identified target AMP-activated protein kinase, which constitutes a novel therapeutic pathway in inflammatory pathology.

Increased Innate Lymphoid Cells in Periodontal Tissue of the Murine Model of Periodontitis: The Role of AMP-Activated Protein Kinase and Relevance for the Human Condition

“…Thus, the interface between inflammation and metabolic changes may be considered as a determinant of immune tolerance. Our inadequate understanding of the relationship between inflammation and metabolism in periodontitis prompted us to explore the impact of the disease on ILCs in the context of assessment of the role of AMPK; AMPK, an archetypal metabolic regulator, is a highly conserved protein kinase that exists in essentially all eukaryotic cells including those of immune system ( 16 , 17 ).…”

“…The advent of AMP-activated protein kinase (AMPK) knockout (KO) mice provides a unique opportunity to explore the impact of AMPK on subtypes of ILCs ( 15 ). This investigation is warranted because while the role of AMPK in cellular bioenergetics is well established, its role in regulation of immune and inflammatory responses is increasing being recognized ( 16 , 17 ). However, the role of AMPK in either periodontitis or its impact on ILCs is not established.…”

Proportion of nonsteroidal anti‐inflammatory drug prescription in equine practice

“…Reasons for this difference are likely to be multiple and further studies are required. The finding of a poor uptake of new NSAIDs in equine veterinary practice is also of interest, particularly in the light of the huge body of research aimed at developing and evaluating new, potentially safer NSAIDs in both human and veterinary science . Whether this applies only to equine practice or to veterinary practice as a whole is unclear at present but may induce some reflection on whether investments should aim at educating practitioners on the prescription of new drugs as well as on the development of new products.…”

Exendin‐4 enhances radiation response of prostate cancer

“…Liraglutide ameliorated palmitate‐induced endothelial dysfunction through activating AMPK and reversing leptin resistance . AMPK has been indicated to play a key role in a series of complex molecular events, far more than in the cell energy metabolism . AMPK is a key sensor of IR signals related to radiation responsiveness .…”