NUC-7738

NUC-7738 is a phosphoramidate prodrug of 3'-deoxyadenosine (cordycepin), designed to overcome the limitations of cordycepin in cancer therapy. Cordycepin is a nucleoside analogue with anticancer properties but suffers from rapid degradation by adenosine deaminase and poor cellular uptake. NUC-7738 uses ProTide technology to bypass these resistance mechanisms, making it resistant to adenosine deaminase and independent of nucleoside transporters for cellular entry. Once inside the cell, it is cleaved by histidine triad nucleotide-binding protein 1 (HINT1) to release active 3'-deoxyadenosine monophosphate, which is further converted into its triphosphate form (3'-dATP). This metabolite terminates DNA and RNA synthesis in cancer cells, leading to apoptosis. Preclinical studies show potent cytotoxicity against both solid tumors and hematological malignancies, with preferential effects on leukemic stem cells. Clinical trials are ongoing for advanced solid tumors and lymphoma[1][4][5][6].

Other names

Fosdesdenosine sipalabenamideL-Alanine, N-(3′-deoxy-P-phenyl-5′-adenylyl)-, phenylmethyl ester (ACI)