RX-3117 (fluorocyclopentenylcytosine) is a novel a cytidine analog. RX-3117 displays anticancer activity in several cancer cell lines, including gemcitabine-resistant variants.

RX-3117 was a very poor substrate for cytidine deaminase (66,000-fold less than gemcitabine). RX-3117 showed a different sensitivity profile compared to cyclopentenyl-cytosine and azacytidine, substrates for uridine-cytidine-kinase. Insensitive U937 cells 1 μM RX-3117 resulted in 90% inhibition of RNA synthesis but 100 μM RX-3117 was required in A2780 and CCRF-CEM cells. RX-3117 at IC50 values did not affect the integrity of RNA [1].

RX-3117 (p.o.) was examined in 9 different human tumor xenograft models grown subcutaneously in athymic nude mice. In the Colo 205, H460, H69 and CaSki models, gemcitabine treatment resulted in 28%, 30%, 25% and 0% tumor growth inhibition (TGI), respectively. Whereas oral treatment with RX-3117 induced 100%, 78%, 62% and 66% TGI, respectively [2].