Rabacfosadine (GS-9219) is a novel dual pre-drug of the acyclic nucleotide phosphonate PMEG to tumor lymphocytes for the study of lymphoma.

Rebaarsen inhibits the proliferation of mitogen-stimulated T and B lymphocytes as determined by BrdUrd binding assay (EC50 135 and 42 nM, respectively). GS-9219 showed strong antiproliferative activity against activated lymphocytes and hematopoietic tumor cell lines. Labafaxadine is converted to its active metabolite, PMEG diphosphate, by enzymatic hydrolysis, deamination and phosphorylation in lymphocytes. In this paper, we investigated the ability of rabafaxadine to inhibit the proliferation of activated lymphocytes and hematopoietic tumor cells. To compare the activity of GS-9219 in dividing and non-dividing cells, the activity of Rabacfosadine in these cell populations was assessed using the metabolism-based XTT sodium assay rather than the BrdUrd assay.The results of the XTT assay showed that the EC50 values of Rabacfosadine differed from those in quiescent (EC50=17.2 μM) and proliferating cells (EC50=135 nM). ) in quiescent cells (EC50=17.2 μM) and proliferating cells (EC50=135 nM) with a 127-fold difference in EC50 values. These results suggest that Rabatadine has a great selectivity for actively replicating lymphoblastoid cells [1].

Rabatadine has potent single-agent activity in dogs with lymphoma by a mechanism of action different from that of doxorubicin. Dogs are treated alternately with rabafenacin (1.0 mg/kg, i.v., weeks 0, 6, and 12) and doxorubicin (30 mg/m2, i.v., weeks 3, 9, and 15). Dogs that achieved a complete response (CR) were evaluated at monthly follow-up visits. Complete clinicopathologic evaluations were performed every 21 days and remission and adverse events (AEs) were assessed. Acute AEs (occurring within 21 days of the first dose of each drug) were compared between labradine and doxorubicin in 46 dogs with at least 1 dose of each drug [2].