Abstract
Namodenoson (CF102, Cl-IB-MECA) is a small, water-insoluble, orally bioavailable highly selective A3 adenosine receptor agonist. Namodenoson exerts its clinical activity by binding to the A3 adenosine receptor, which has a role in both inflammation and cancer and was shown to be highly expressed on cancer and inflammatory cells. Namodenoson is currently under clinical development as a treatment for hepatocellular carcinoma (phase 3 trial is ongoing) and metabolic dysfunction-associated steatohepatitis (phase 2b trial is ongoing). Beyond the liver, namodenoson has also been shown to provide protective effects in the central nervous system and the cardiovascular system. The protective effects of namodenoson include anti-ischemic, anti-inflammatory, anti-toxicity, and anti-fibrotic effects. Adiponectin is a hormone produced by adipocytes. It is a polypeptide containing 244 amino acids and can be found in 3 forms (low, moderate, and high molecular weight). It binds to 3 receptors: adiponectin receptor 1, adiponectin receptor 2, and T-cadherin. Adiponectin plays protective roles in a variety of physiological functions across many organs, including the central nervous system, cardiovascular system, and the liver, as well as the kidneys, muscles, and bones. Similar to namodenoson, adiponectin provides anti-ischemic, anti-inflammatory, as well as anti-fibrotic protection, but it is also involved in energy regulation, protection against oxidative stress, promotion of insulin sensitivity, and more. The current review discusses the protective effects of namodenoson in the central nervous system, cardiovascular system, and liver focusing on the available preclinical evidence supporting such protective effects in each system, and presents evidence from preclinical models and translational data from the phase 2 trial in metabolic dysfunction-associated steatohepatitis supporting the hypothesis that namodenoson’s protective effects are mediated via pathways that involve adiponectin.