566TiP A first-in-human study of NUC-7738, a ProTide transformation of 3’-deoxyadenosine, in patients with advanced solid tumours (NuTide:701)

NUC-7738 is a phosphoramidate transformation of 3’-deoxyadenosine (3’-dA or cordycepin), a derivative of adenosine that was first isolated from Cordyceps sinensis. Although 3’-dA has potent in vitro anti-tumour activity, it has not been successfully developed in the clinic as an anti-cancer agent due primarily to its rapid breakdown by adenosine deaminase (ADA). Although the cytotoxic activity of 3’-dA is largely attributed to intracellular generation of the triphosphate metabolite, 3’-dATP, (inhibition of RNA and DNA synthesis) additional in vitro effects have also been attributed to 3’-dAMP and 3’-dADP.