cPrPMEDAP, an intermediate metabolite of GS-9219, acts as a prodrug for the guanine nucleotide analog PMEG, demonstrating antiproliferative activity. It is negatively charged at physiological pH, resulting in poor skin permeability.

cPrPMEDAP displays antiproliferative properties against SiHa cells (HPV-transformed cervical carcinoma cell lines) with an EC50 value of 290 nM[1]. Its counterpart, PMEG, generates an active phosphorylated metabolite, PMEG diphosphate (PMEG-DP), which effectively inhibits growth in various transformed cell lines by strongly suppressing nuclear DNA polymerases α, δ, and ?, thus hindering DNA synthesis and/or repair. Although PMEG demonstrates antiproliferative efficacy in animal models, its application as an antiproliferative agent is constrained by its limited cellular uptake and pronounced toxicity. cPrPMEDAP, on the other hand, exhibits comparable in vitro antiproliferative effectiveness and diminished toxicity in vivo. However, similar to PMEG, it faces challenges with skin permeability due to its negative charge at physiological pH[1].