Uridine triacetate is used to treat an overdose of capecitabine or fluorouracil. In addition, it is used as a pyrimidine analog for uridine replacement indicated for the treatment of hereditary orotic aciduria. Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation. Uridine competitively inhibits cell damage and cell death caused by fluorouracil. Uridine can be used by essentially all cells to make uridine nucleotides, compensating for the genetic deficiency in synthesis in patients with hereditary orotic aciduria. When intracellular uridine nucleotides are restored into the normal range, overproduction of orotic acid is reduced by feedback inhibition, so that urinary excretion of orotic acid is also reduced. Adverse reactions occurring in >2% of patients receiving uridine triacetate included vomiting, nausea, and diarrhea. In vitro data showed that uridine triacetate was a weak substrate for P-glycoprotein. Due to the potential for high local (gut) concentrations of the drug after dosing, the interaction of uridine triacetate with orally administered P-gp substrate drugs cannot be ruled out.

Cladribine is used for the treatment of hairy cell leukemia and multiple sclerosis (MS). As a purine analog, it is a synthetic anti-cancer agent that also suppresses the immune system. Chemically, it mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA. It can be distinguished from other chemotherapeutic agents affecting purine metabolism in that it is cytotoxic to both actively dividing and quiescent lymphocytes and monocytes, inhibiting both DNA synthesis and repair. Cladribine injection is a potent antineoplastic agent with potentially significant toxic side effects. In MS, the novel mechanism of action of cladribine is expected to reduce inflammation, autoimmune effects and autoreactive cell damage, thereby improving the integrity of the blood–brain barrier. Thus, the effects of cladribine may target some of the key events that are central to the pathophysiology of MS.

Binodenoson, a selective adenosine A(2A) receptor agonist, was being developed as a short-acting coronary vasodilator as an adjunct to radiotracers for use in myocardial stress imaging. Binodenoson for injection under the brand name CorVue was developed for use in patients with or at risk for coronary artery disease (CAD) who are unable to perform a cardiac exercise stress test. CorVue was designed to minimize side effects such as dyspnea, flushing, heart block, and chest pain. Binodenoson did not achieve FDA approval in 2009 due to concerns over equivalence of its efficacy with adenosine.

Piclidenoson (CF101), generically known as IB-MECA (methyl 1-[N6-(3-iodobenzyl)-adenin-9-yl]-b-D-ribofuronamide), is an oral small molecule drug formulated in a tablet. The activity of CF101 as an anti-inflammatory agent has been tested in a number of different experimental models including adjuvant and collagen induced arthritis and inflammatory bowel disease. CF101 is a highly specific agonist at the A3AR known to induce a robust anti-inflammatory effect in different experimental animal models. The CF101 mechanism of action entails down-regulation of the NF-κB-TNF-α signaling pathway, resulting in inhibition of pro-inflammatory cytokine production and apoptosis of inflammatory cells. Piclidenoson is currently being developed for the treatment of autoimmune inflammatory diseases like RA and psoriasis, hoping to replace the current standard of care, methotrexate (MTX). Can-Fite has tested CF101 in a number of Phase II studies in different diseases. A Phase II study in Psoriasis successfully met its primary endpoint showing that CF101 effectively ameliorated disease symptoms. In an interim analysis of the Phase II/III study the data justified full enrollment of the study. Phase II studies in Rheumatoid Arthritis (RA) demonstrated efficacy of CF101 given as a monotherapy. Moreover, a direct correlation between A3AR at baseline and patients’ response to CF101, suggesting its utilization as a predictive biomarker. Piclidenoson is headed into Phase 3 trials for RA and psoriasis.

8-chloroadenosine (8-Cl-Ado) is a ribonucleoside analog. The mechanism of its action remains poorly understood, however, it is known that the drug inhibits RNA synthesis. It has significant cytotoxic activity against lymphoid and myeloid malignant cells. The nucleoside analog 8-Cl-Ado is phosphorylated into its cytotoxic triphosphate 8-Cl-ATP. The accumulation of the cytotoxic metabolite results in a parallel decrease of the ATP cellular pools. 8-Cl-Ado gets incorporated into RNA during transcription, hindering this process. In addition, this triphosphate inhibits ATP-dependent poly(A) tail synthesis, and, as a consequence, mRNA processing is inhibited, resulting in vitro cytotoxicity in several solid and hematological malignancies. This agent is currently in clinical trials for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia.

CF102 known as Cl-IB-MECA (2-chloro-N6-(3-iodobenzyl)-adenosine-5’- N-methyl-uronamide), is a highly specific and selective agonist at the A3 adenosine receptor. Phase I/II study in hepatocellular carcinoma (HCC) successfully met its primary and secondary endpoints demonstrating initial indications for efficacy of CF102. A global Phase II study treating patients with CF102 as a second line therapy will start enroling patients shortly.