Dr. Cho-Chung from the NIH first thought to use halogenated cAMP derivatives as competitive inhibitors of cAMP to slow down cancer cell mitosis. While the iodine and bromine substituted versions showed very little therapeutic actions, 8-Chloro cAMP has been shown to have strong anti-cancer effects. This has been shown in the phase II clinical trials this drug has undergone. However, these trials have had issues with solubility and toxicity. The drug is similar to vitamin C and is excreted quickly. Scientists tried to overcome this by using a peristaltic pump to give patients a continuous dosage, but this proved too toxic for patients, leading to the denial of phase III trials. However, this may be overcome by taking advantage of another drug. 8-Cl Adenosine, a drug currently in phase I clinical trials, is metabolized in the body to 8-Cl ATP which is further metabolized to 8-Cl cAMP. This is important as 8-Cl Adenosine is thus not only a prodrug for 8-Cl cAMP but it is also less soluble meaning its concentrations remain high in the body for longer periods of time. Therefore, lowering the dosage of 8-Cl-cAMP and adding an IV dosage of 8-Cl Adenosine would not only provide patients with the enhanced anti-cancer effects but also give the body a less toxic source of 8-Cl cAMP in the form of 8-Cl Adenosine. We believe that combination therapy using both 8-Cl cAMP and 8-Cl Adenosine can operate synergistically, provide better anti-cancer effects, and are thus prime targets for clinical trials.
Munoz, Erik; Saich, Andrea; Cox, Andrew; and Chang, Yu-An Peter, "Clinical Applications of a Combination Chemotherapy Using 8-Chloro cAMP and 8-Chloro Adenosine" (2015). Student Research Day Abstracts and Posters. 111.