Rabacfosadine is a novel prodrug of the nucleotide analogue PMEG and is designed as a cytotoxic agent.

Rabacfosadine inhibits the proliferation of mitogen-stimulated T and B lymphocytes (EC50: 135 and 42 nM, respectively), as determined by BrdUrd incorporation. GS-9219 has substantial antiproliferative activity against activated lymphocytes and hematopoietic tumor cell lines. Rabacfosadine is converted to its active metabolite in lymphocytes, PMEG diphosphate, via enzymatic hydrolysis, deamination, and phosphorylation. The ability of Rabacfosadine to inhibit the proliferation of activated lymphocytes and of tumor cells of hematopoietic origin is investigated. To compare the activity of GS-9219 in dividing and nondividing cells, Rabacfosadine is evaluated in these populations using a metabolism-based sodium XTT assay instead of BrdUrd assays. Results from the XTT assay displays a 127-fold difference between the EC50 values of Rabacfosadine in quiescent (EC50=17.2 μM) and proliferating (EC50=135 nM) cells. These results indicate a substantial selectivity of Rabacfosadine toward actively replicating lymphoblasts [1].

Rabacfosadine has substantial single-agent activity in dogs with lymphoma, and a different mechanism of action than Doxorubicin. Dogs receive alternating Rabacfosadine (1.0 mg/kg IV weeks 0, 6, 12) and Doxorubicin (30 mg/m2 IV weeks 3, 9, 15). Dogs that achieved a complete response (CR) are followed by monthly evaluations. Complete clinicopathological evaluation and assessment of remission and adverse event (AEs) are performed every 21 days. Acute AEs, occurring within 21 days after administration of the first dose of each agent, are compared between Rabacfosadine and Doxorubicin in 46 dogs receiving at least 1 dose of each agent [2].

859209-74-8

C21H35N8O6P

526.53

GS-9219;VDC-1101;Rabacfosadine

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years