Adenosine is an endogenous nucleoside that regulates many physiological and pathological processes. It is derived from either the intracellular or extracellular dephosphorylation of adenosine triphosphate and interacts with cell-surface G-protein-coupled receptors. Adenosine plays a substantial role in protecting against cell damage in areas of increased tissue metabolism and preventing organ dysfunction in pathological states. Targeting adenosine metabolism and receptor signaling may be an effective therapeutic approach for human diseases, including cardiovascular and central nervous system disorders, rheumatoid arthritis, asthma, renal diseases, and cancer. Several lines of evidence have shown that many drugs exert their beneficial effects by modulating adenosine signaling pathways but this knowledge urgently needs to be summarized, and most importantly, actualized. The present review collects pharmaceuticals and pharmacological or diagnostic tools that target adenosine signaling in their primary or secondary mode of action. We overviewed FDA-approved drugs as well as those currently being studied in clinical trials. Among them are already used in clinic A2A adenosine receptor modulators like istradefylline or regadenoson, but also plenty of anti-platelet, anti-inflammatory, or immunosuppressive, and anti-cancer drugs. On the other hand, we investigated dozens of specific adenosine pathway regulators that are tested in clinical trials to treat human infectious and noninfectious diseases. In conclusion, targeting purinergic signaling represents a great therapeutic challenge. The actual knowledge of the involvement of adenosinergic signaling as part of the mechanism of action of old drugs has open a path not only for drug-repurposing but also for new therapeutic strategies.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2023.115184DOI Listing

Publication Analysis

Top Keywords

adenosine signaling
12
adenosine
9
targeting adenosine
8
signaling pathways
8
clinical trials
8
signaling
6
drugs
5
drugs targeting
4
pathways current
4
current view
4

Similar Publications

Activation of PLCβ enzymes by G and G proteins is a common mechanism to trigger cytosolic Ca increase. We and others reported that G inhibitor FR900358 (FR) can inhibit both and G - and, surprisingly, G -mediated intracellular Ca mobilization. Thus, the G -G -PLCβ-Ca signaling axis depends entirely on the presence of active G , which reasonably explained FR-inhibited G -induced Ca release.

View Article and Find Full Text PDF

Baicalein tethers CD274/PD-L1 for autophagic degradation to boost antitumor immunity.

Autophagy

December 2024

Institute of Energy Metabolism and Health, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Immune checkpoint inhibitors, especially those targeting CD274/PD-L1yield powerful clinical therapeutic efficacy. Thoughmuch progress has been made in the development of antibody-basedCD274 drugs, chemical compounds applied for CD274degradation remain largely unavailable. Herein,baicalein, a monomer of traditional Chinese medicine, isscreened and validated to target CD274 and induces itsmacroautophagic/autophagic degradation.

View Article and Find Full Text PDF

Salt-inducible kinases (SIKs) in cancer: mechanisms of action and therapeutic prospects.

Drug Discov Today

December 2024

Cell Signaling and Cancer Biology Laboratory, Department of Biochemistry, Guindy Campus, University of Madras, Chennai 600025, India. Electronic address:

Salt-inducible kinases (SIKs), a group of serine/threonine kinases in the adenosine monophosphate-activated protein kinase (AMPK) family, exist in three isoforms: SIK1, SIK2 and SIK3. These kinases are crucial in various physiological processes. Emerging evidence indicates that dysregulation of SIK expression and activation significantly contributes to carcinogenesis by promoting cellular proliferation, metabolic dysregulation, metastasis and chemoresistance through the modulation of crucial signaling pathways.

View Article and Find Full Text PDF

Reactive oxygen species-mediated signal transduction and utilization strategies in microalgae.

Bioresour Technol

December 2024

Yunnan Urban Agricultural Engineering & Technological Research Center, College of Agriculture and Life Science, Kunming University, Kunming 650214, PR China. Electronic address:

Reactive oxygen species (ROS) are crucial in stress perception, the integration of environmental signals, and the activation of downstream response networks. This review emphasizes ROS-mediated signaling pathways in microalgae and presents an overview of strategies for leveraging ROS. Eight distinct signaling pathways mediated by ROS in microalgae have been summarized, including the calcium signaling pathway, the target of rapamycin signaling pathway, the mitogen-activated protein kinase signaling pathway, the cyclic adenosine monophosphate/protein kinase A signaling pathway, the ubiquitin/protease pathway, the ROS-regulated transcription factors and enzymes, the endoplasmic reticulum stress, and the retrograde ROS signaling.

View Article and Find Full Text PDF

Aims: NAD deficiency underlies obesity-induced metabolic disturbances. This study evaluated dihydronicotinamide riboside (NRH), a potent NAD enhancer, in lean and obese mice and explored whether NRH operates through a unique mechanism involving adenosine kinase (ADK), an enzyme critical for NRH-driven NAD synthesis.

Methods: Pharmacokinetic and pharmacodynamic analyses were performed following a single 250 mg/kg intraperitoneal injection of NRH in healthy mice.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!