Purines are heterocyclic aromatic compounds composed of linked pyrimidine and imidazole rings. In mammals, purines are most commonly expressed in DNA and RNA (including the purines adenine and guanine), as well as single-molecule nucleotides (adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), cyclic AMP, and to a lesser extent guanosine triphosphate (GTP) and cyclic guanosine monophosphate (cGMP). Purines are also key elements of the following energy metabolism molecules: reduced nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate (NADPH), and coenzyme Q. Purines can also act as direct neurotransmitters; for example, adenosine may interact with receptors to modulate cardiovascular and central nervous system (CNS) function.
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Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson was evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).
Namodenoson granted Orphan Drug and Fast track status from the FDA. A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.
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